Honeybee repellents and uses thereof

ABSTRACT

The present specification discloses honeybee repellents exhibiting repellent properties similar to 2-heptanone, compositions comprising such repellents, uses to repel a honeybee from a mammal, location, plant, structure treated of such repellents, and methods of treating a mammal, location, plant, structure by applying such repellents.

This continuation application claims the benefit of priority and thefiling date pursuant to 35 U.S.C. 120 to U.S. patent application Ser.No. 14/115,800, filed Jan. 17, 2014, a 35 U.S.C. § 371 National StageFiling of International Patent Application PCT/US0012/036670, filed May4, 2012, which claims priority to U.S. Provisional Patent Application61/495,639, filed Jun. 10, 2011, and U.S. Provisional Patent Application61/482,995, filed May 5, 2011, each of which is hereby incorporated byreference I its entirety.

Honeybees use scent marks while foraging. When collecting nectar and/orpollen, foraging honeybees scent mark nectar-producing flower bydepositing attractive pheromones to signal to other honeybees of anearby rewarding food source. Honeybees also use a short-lived repellentscent mark that identifies exhausted and recently visited rewardingflowers not yet replenished with nectar. Subsequently visiting honeybeesdetect and avoid these nectar-depleted flowers. Over time, as nectarreplenishes in the flower, the repellent scent mark fades until gone andthe flower is eventually revisited by another foraging honeybee. It ispresumed that the use of repellent scent marks increases foragingefficiency by reducing the time spent probing nectar-depleted flowers.

The repellent scent mark used by honeybees is 2-heptanone. Produced andsecreted by the mandibular glands of adult worker honey bees,2-heptanone is known as the alarm pheromone because under certaincircumstances elicits aggressive behavior in honeybees when detected.Honeybees detect 2-heptanone using an olfactory pathway mediated by aspecific odorant-binding protein called OBP2. By taking advantage of itsproperties, repellent formulation of 2-heptanone have been produced andused in agricultural settings. For example, 2-heptanone has been appliedto crops in order to repel honeybees away from areas where toxicinsecticides have also been applied, thereby reducing honeybee mortalityand avoiding potential insecticide contamination of the colony and thehive products obtained thereof. However, such uses have had very limitedsuccess primarily because 2-heptanone is a considerably volatilecompound, having an effective half-life of only a few hours. As such,2-heptanone is impractical and cost-ineffective for agricultural usesbecause of the extensive efforts necessary to apply and maintain aneffective amount of this repellent in the treated area.

Therefore, what are needed are more effective honeybee repellents thatexhibit repellent properties similar to 2-heptanone, but are lessvolatile. The present specification discloses such honeybee repellentsand uses and methods for such compounds. The disclosed honeybeerepellents will benefit apiculture since honeybees are a crucial,domesticated species that is threatened by routine agriculturalpractices such as the use of insecticides.

Thus, aspects of the present specification disclose honeybee repellentsexhibiting repellent properties similar to 2-heptanone, but are lessvolatile than 2-heptanone.

Other aspects of the present specification disclose a use of a honeybeerepellent disclosed herein to repel a honeybee from a location treatedwith the honeybee repellent. In one embodiment, the disclosed use is ause of a honeybee repellent disclosed herein to repel a honeybee fromforaging and/or collecting nectar from a flower of a plant treated withthe honeybee repellent. In another embodiment, the disclosed use is ause of a honeybee repellent disclosed herein to repel a honeybee from astructure treated with the honeybee repellent.

Yet other aspects of the present specification disclose a method oftreating a location by applying a honeybee repellent disclosed herein,wherein the application repels a honeybee from the treated location. Inone embodiment, the disclosed method is a method of treating a plant byapplying a honeybee repellent disclosed herein, wherein such applicationrepels a honeybee from foraging and/or collecting nectar from a flowerof the treated plant. In another embodiment, the disclosed method is amethod of treating a structure by applying a honeybee repellentdisclosed herein, wherein such application repels a honeybee from thetreated structure.

DESCRIPTION

Honeybees are maintained by humans in order to harvest honey, beeswax,and other hive products produced by these insects for commercialmarkets. In the United States, for example, honeybees produce $270million worth of honey, beeswax, and other hive products. Besides theeconomic importance of hive products, honeybees are critically necessaryto pollinate many important agricultural crops produced worldwide. Forexample, honeybees pollinate over $14 billion worth of crops annually inthe United States. As such, promoting and maintaining honeybee survivalis of great economic importance.

Insecticides are widely used to increase the yields of agriculturalcrops and their use is one of the major factors behind the increase inagricultural productivity in the 20th century. However, there is aninherent tension between the use of insecticides on crop plants tocontrol invading pest insects and the necessity of honeybees topollinate these same plants and the economic importance of hiveproducts. One commonly used method is to delay the use of insecticidesuntil the honeybees pollination has occurred, and then apply theinsecticide. However, foraging for nectar occurs throughout the growingseason, and as such, foraging honeybees are still exposed to theinsecticide. Furthermore, recent evidence suggests that commonly usednicotine-based insecticides like Clothianidin and Imidacloprid may be acausal factor in colony collapse disorder, a phenomenon in which workerhoneybees from a colony abruptly disappear. As such, it would beextremely beneficial to develop and use compounds and methods of insectcontrol that minimize honeybee mortality.

Although of significant value, honeybee pollination can also causeeconomic harm to certain agricultural crops. For example, certainseedless citrus fruits like seedless tangerines, grapefruit, andmandarin oranges are of great economic value due to consumer preference.These seedless fruits are self-pollinating. However, if honeybeescross-pollinate the crop plants with the pollen of a seeded citrusfruit, then these citrus fruits will develop seeds and becomeundesirable to the consumer. As such, citrus fruit growers employinsecticides in order to prevent honeybee cross-pollination. The mostcommon insecticides used for this application are neonicotinoids likeClothianidin and Imidacloprid, which as discussed above, appears to be acausal factor in colony collapse disorder. One problem with thisapproach is that the nectar collected by honeybees from the flowers ofcitrus trees produces a flavorful and economically desirable honey. Assuch, beekeepers have historically kept colonies near citrus orchards.Thus, there is another inherent tension between the economic importanceof hive products produced by honeybees versus the financial harm causedby honeybee pollination in certain agricultural crops like citrus trees.As such, it would be extremely beneficial to develop and use compoundsand methods that could repel honeybees from crop plants wherepollination is undesired without causing significant honeybee mortality.

Insect chemosensory proteins (CSPs) regulate or control crucialbehaviors. The chemosensory system consists of several chemosensoryprotein (CSP) classes. Chemosensory protein classes that are importantin the design of novel insect control products include soluble proteinsfound in the antennal hemolymph and the maxillary palps, such as odorantbinding proteins (OBPs) and sensory appendage proteins (SAPs). OBPs andSAPs are carrier proteins that facilitate the transport of externalstimuli such as odor molecules through the aqueous hemolymph of sensoryappendages to the surfaces of neuronal cells. There, the protein/odorantmolecule complexes bind G-protein coupled receptors (GPCRs) and initiatea signaling cascade that results in a behavioral response to theexternal odor or stimulus. Insects use chemosensory cues from theenvironment to control critical behaviors, such as feeding and mating.Thus, insect chemosensory proteins are promising targets for thediscovery of novel insect control products based on manipulating insectbehavior.

The present specification discloses improved honeybee repellents anduses and methods for such repellents. By exploiting the OBP2 olfactorypathway used by 2-heptanone, more effective repellent compounds havebeen identified and isolated. As such, the repellents disclosed hereinmanipulate the honeybees' chemosensory system by eliciting an avoidanceresponse similar to the one initiated by 2-heptanone. The repellentsdisclosed herein are intended for agricultural, commercial, and consumeruse. For example, the honeybee repellents disclosed herein are useful torepel honeybees from areas where insecticides have also been applied inorder to reduce honeybee mortality and avoid insecticide contaminationof honey, beeswax, and other hive products. As another non-limitingexample, the honeybee repellents disclosed herein are useful to preventunwanted pollination of plants by honeybees in crops where suchpollination reduces the market value due to the resulting seeded fruits.As yet another non-limiting example, the honeybee repellents disclosedherein are useful to keep away honeybees from outdoor areas where humanactivities are occurring and would be disrupted by honeybee presence,such as, e.g., an outdoor activity like a sporting event or picnic.Similarly, the honeybee repellents disclosed herein are useful to keepaway honeybees from man-made structures in order to prevent infestationof a colony, such as, e.g., a commercial building, a house, a shed, orother structure. Other uses of the honeybee repellents disclosed hereinare discussed below and are readily apparent to a person of ordinaryskill.

Aspects of the present specification disclose a honeybee repellent. Asused herein, the term “honeybee repellent” is synonymous with “repellentcompound” and refers to a compound that mimics a 2-heptanone-specificresponse. 2-Heptanone, CH₃(CH₂)₄COCH₃, CAS Registry No. 110-43-0, alsoknown as methyl n-amyl ketone and methyl pentyl ketone, is a colorless,liquid with a banana-like, fruity odor. It is a volatile liquid at roomtemperature [d415 0.8197; b.p.₇₆₀ 151.5 OC.] and soluble in alcohol orether and very slightly soluble in water. 2-Heptanone is availablecommercially.

Bees are insects of the Order Hymenoptera, Superfamily Apoidea, andcomprise a group of about 20,000 species that live throughout the world.Examples of common bees are honeybees (Apis), bumble bees (Bomzbus),small carpenter bees (Ceratina), large carpenter bees (Xylocopa), paperwasps (Polistes), yellow jackets (Vespula), and baldfaced hornets(Vespula). At least seven species of honeybee are commonly recognizedwith a total of 44 subspecies and various strains, varieties, andhybrids thereof. As used herein, the term “honeybee” refers to anymember of the Order Hymeoptera, Family Apidae, and includes, withoutlimitation, Apis andreniformis, Apis cerana, Apis dorsata, Apis florae,Apis koschevnikovi, Apis laboriosa, Apis mellifera, Apis nigrocincta,Apis rorea, subspecies thereof, and strains, varieties, and hybridsthereof.

In one embodiment, a honeybee repellent disclosed herein substantiallymimics the attractant chemosensory cues of a natural compound producedby a plant or plant part like a flower. In an aspect of this embodiment,a honeybee repellent disclosed herein substantially mimics a repellentchemosensory cue of 2-heptanone.

In aspects of this embodiment, a honeybee repellent disclosed herein hasa repellent chemosensory cue that is, e.g., about 75%, about 80%, about85%, about 90%, about 95%, about 97%, or about 100% that of therepellent chemosensory cue of 2-heptanone. In other aspects of thisembodiment, a honeybee repellent disclosed herein has a repellentchemosensory cue that is, e.g., at least 75%, at least 80%, at least85%, at least 90%, at least 95%, or at least 97% that of the repellentchemosensory cue of 2-heptanone. In other aspects of this embodiment, ahoneybee repellent disclosed herein has a repellent chemosensory cuethat is between, e.g., about 75% to about 97%, about 80% to about 97%,about 85% to about 97%, about 90% to about 97%, about 75% to about 100%,about 80% to about 100%, about 85% to about 100%, or about 90% to about100% that of the repellent chemosensory of 2-heptanone.

In an embodiment, a honeybee repellent disclosed herein has a repellentchemosensory cue that is, e.g., at least one-fold, at least two-fold, atleast three-fold, at least four fold, at least five-fold, at leastsix-fold, at least seven-fold, at least eight-fold, at least nine-fold,at least 10-fold, at least 20-fold, at least 30-fold, at least 40-fold,at least 50-fold, at least 60-fold, at least 70-fold, at least 80-fold,at least 90-fold, at least 100-fold, at least 125-fold, at least150-fold, at least 175-fold, or at least 200-fold that of the repellentchemosensory cue of 2-heptanone.

In an embodiment, a honeybee repellent disclosed herein has a honeybeerepellency activity. In aspects of this embodiment, presence of ahoneybee repellent repels honeybees by, e.g., at least 10%, at least15%, at least 20%, at least 25%, at least 30%, at least 35%, at least40%, at least 45%, at least 50%, at least 55%, at least 60%, at least65%, at least 70%, at least 75%, at least 80%, at least 85%, at least90%, or at least 95%, as compared to not having the honeybee repellentpresent. In other aspects of this embodiment, presence of a honeybeerepellent repels honeybees by, e.g., about 10% to about 100%, about 20%to about 100%, about 30% to about 100%, about 40% to about 100%, about50% to about 100%, about 60% to about 100%, about 70% to about 100%,about 80% to about 100%, about 10% to about 90%, about 20% to about 90%,about 30% to about 90%, about 40% to about 90%, about 50% to about 90%,about 60% to about 90%, about 70% to about 90%, about 10% to about 80%,about 20% to about 80%, about 30% to about 80%, about 40% to about 80%,about 50% to about 80%, or about 60% to about 80%, about 10% to about70%, about 20% to about 70%, about 30% to about 70%, about 40% to about70%, or about 50% to about 70%, as compared to not having the honeybeerepellent present.

In an embodiment, a honeybee repellent disclosed herein reduces ahoneybee interaction with a mammal, a plant, structure, and/or location.In aspects of this embodiment, a honeybee repellent reduces honeybeeinteraction with a mammal, plant, structure, and/or location by, e.g.,at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, atleast 35%, at least 40%, at least 45%, at least 50%, at least 55%, atleast 60%, at least 65%, at least 70%, at least 75%, at least 80%, atleast 85%, at least 90%, or at least 95%. In other aspects of thisembodiment, a honeybee repellent reduces honeybee interaction with amammal, a plant, structure, and/or location by, e.g., about 10% to about100%, about 20% to about 100%, about 30% to about 100%, about 40% toabout 100%, about 50% to about 100%, about 60% to about 100%, about 70%to about 100%, about 80% to about 100%, about 10% to about 90%, about20% to about 90%, about 30% to about 90%, about 40% to about 90%, about50% to about 90%, about 60% to about 90%, about 70% to about 90%, about10% to about 80%, about 20% to about 80%, about 30% to about 80%, about40% to about 80%, about 50% to about 80%, or about 60% to about 80%,about 10% to about 70%, about 20% to about 70%, about 30% to about 70%,about 40% to about 70%, or about 50% to about 70%.

In an embodiment, a honeybee repellent disclosed herein reduces anability of a honeybee to obtain a meal and/or nectar from a plant. Inaspects of this embodiment, a honeybee repellent reduces an ability of ahoneybee to obtain a meal from a plant by, e.g., at least 10%, at least15%, at least 20%, at least 25%, at least 30%, at least 35%, at least40%, at least 45%, at least 50%, at least 55%, at least 60%, at least65%, at least 70%, at least 75%, at least 80%, at least 85%, at least90%, or at least 95%. In other aspects of this embodiment, a honeybeerepellent reduces an ability of a honeybee to obtain a meal and/ornectar from a plant by, e.g., about 10% to about 100%, about 20% toabout 100%, about 30% to about 100%, about 40% to about 100%, about 50%to about 100%, about 60% to about 100%, about 70% to about 100%, about80% to about 100%, about 10% to about 90%, about 20% to about 90%, about30% to about 90%, about 40% to about 90%, about 50% to about 90%, about60% to about 90%, about 70% to about 90%, about 10% to about 80%, about20% to about 80%, about 30% to about 80%, about 40% to about 80%, about50% to about 80%, or about 60% to about 80%, about 10% to about 70%,about 20% to about 70%, about 30% to about 70%, about 40% to about 70%,or about 50% to about 70%.

A honeybee repellant disclosed herein may be more stable (or lessvolatile) than 2-heptanone. In aspects of this embodiment, a honeybeerepellant disclosed herein has a half-life of, e.g., about one day,about three days, about five days, about one week, about two weeks,about three weeks, about one month, about two months, or about threemonths. In other aspects of this embodiment, a honeybee repellantdisclosed herein has a half-life of, e.g., at least one day, at leastthree days, at least five days, at least one week, at least two weeks,at least three weeks, at least one month, at least two months, or atleast three months. In yet other aspects of this embodiment, a honeybeerepellant disclosed herein has a half-life of between, e.g., about oneday to about seven days, about three days to about seven days, aboutfive days to about seven days, about one week to about four weeks, abouttwo weeks to about four weeks, about three weeks to about four weeks,about one month to about four months, about two months to about fourmonths, or about three months to about four months.

A honeybee repellent may preferentially bind, without limitation, anodorant Binding Protein 2 (OBP2). OBP2, also known as ASP2, refers to asoluble, acidic protein of about 13-16 kDa that is expressed in sensorytissues of honeybees. This protein binds 2-heptanone and escorts thiscompound across the hydrophilic extracellular matrix to the cellsurface, where odorant receptors are located. Exemplary honeybee OBP2sinclude, without limitation, Apis mellifera OBP2 (SEQ ID NO: 1) and Apiscerana OBP2 (SEQ ID NO: 2). For a general review see, e.g., Dani, etal., Mapping the Expression of Soluble Olfactory Proteins in theHoneybee, J. Proteome Res. 9(4): 1822-1833 (2010); Pelosi, et al.,Soluble Proteins in Insect Chemical Communication, Cell. Mol. Life Sci.63(14): 1658-1676 (2006); Calvello, et al., Expression ofOdorant-Binding Proteins and Chemosensory Proteins in Some Hymenoptera,Insect Biochem. Mol. Biol. 35(4): 297-307 (2005), each of which ishereby incorporated by reference in its entirety.

A honeybee repellent disclosed herein may be characterized by it bindingaffinity. Binding affinity can be described by an equilibriumdissociation constant (KD), which is defined as the ratio Kd/Ka atequilibrium; where Ka is the association rate constant of the repellentcompound and kd is the dissociation rate constant of the repellentcompound. Binding affinity is determined by both the association and thedissociation and alone neither high association or low dissociation canensure high affinity. The association rate constant (Ka), or on-rateconstant (Kon), measures the number of binding events per unit time, orthe propensity of the repellent compound and the honeybee OBP toassociate reversibly into its repellent-OBP complex. The associationrate constant is expressed in M⁻¹ s⁻¹. The larger the association rateconstant, the more rapidly the repellent compound binds to its honeybeeOBP, or the higher the binding affinity between repellent compound andhoneybee OBP. The dissociation rate constant (Kd), or off-rate constant(Koff), measures the number of dissociation events per unit timepropensity of a repellent-OBP complex to separate (dissociate)reversibly into its component molecules, namely the repellent compoundand the honeybee OBP. The dissociation rate constant is expressed ins⁻¹. The smaller the dissociation rate constant, the more tightly boundthe repellent compound is to its honeybee OBP, or the higher the bindingaffinity between repellent compound and honeybee OBP. The equilibriumdissociation constant (KD) measures the rate at which new repellent-OBPcomplexes formed equals the rate at which repellent-OBP complexesdissociate at equilibrium. The equilibrium dissociation constant isexpressed in M, and is defined as Koff/Kon=[L]×[R]/[L+R], where [L] isthe molar concentration of the repellent compound, [R] is the molarconcentration of the honeybee OBP, and [L+R] is the molar concentrationof the repellent-OBP complex, where all concentrations are of suchcomponents when the system is at equilibrium. The smaller theequilibrium dissociation constant, the more tightly bound the repellentcompound is to its honeybee OBP, or the higher the binding affinitybetween repellent compound and honeybee OBP.

In an embodiment, a honeybee repellent disclosed herein has a bindingaffinity that is substantially the same as the binding affinity of thenatural ligand for that honeybee OBP. In aspects of this embodiment, ahoneybee repellent disclosed herein has a binding affinity for ahoneybee OBP that is, e.g., about 75%, about 80%, about 85%, about 90%,about 95%, about 97%, or about 100% that of the binding affinity of thenatural ligand for that honeybee OBP. In other aspects of thisembodiment, a honeybee repellent disclosed herein has a binding affinityfor a honeybee OBP that is, e.g., at least 75%, at least 80%, at least85%, at least 90%, at least 95%, or at least 97% that of the bindingaffinity of the natural ligand for that honeybee OBP. In other aspectsof this embodiment, a honeybee repellent disclosed herein has a bindingaffinity for a honeybee OBP that is between, e.g., about 75% to about97%, about 80% to about 97%, about 85% to about 97%, about 90% to about97%, about 75% to about 100%, about 80% to about 100%, about 85% toabout 100%, or about 90% to about 100% that of the binding affinity ofthe natural ligand for that honeybee OBP.

In an embodiment, the binding affinity of a honeybee repellent thatbinds to a honeybee OBP has a dissociation equilibrium constant that isgreater than the dissociation equilibrium constant of the natural ligandfor that honeybee OBP. In aspects of this embodiment, the bindingaffinity of a honeybee repellent that binds to a honeybee OBP has adissociation equilibrium constant that is greater than the dissociationequilibrium constant of the natural ligand for that honeybee OBP by,e.g., at least one-fold, at least two-fold, at least three-fold, atleast four fold, at least five-fold, at least six-fold, at leastseven-fold, at least eight-fold, at least nine-fold, at least 10-fold,at least 20-fold, at least 30-fold, at least 40-fold, at least 50-fold,at least 60-fold, at least 70-fold, at least 80-fold, at least 90-fold,at least 100-fold, at least 125-fold, at least 150-fold, at least175-fold, or at least 200-fold.

In another embodiment, a honeybee repellent disclosed herein binds to ahoneybee OBP with binding affinity having an association rate constantof, e.g., less than 1×10⁵ M⁻¹ s⁻¹, less than 1×10⁶ M⁻¹ s⁻¹, less than1×10⁷ M⁻¹ s⁻¹, or less than 1×10⁸ M⁻¹ s⁻¹. In another embodiment, ahoneybee repellent disclosed herein binds to a honeybee OBP with bindingaffinity having an association rate constant of, e.g., more than 1×10⁵M⁻¹ s⁻¹, more than 1×10⁶ M⁻¹ s⁻¹, more than 1×10⁷ M⁻¹ s⁻¹, or more than1×10⁸M⁻¹ s⁻¹. In another embodiment, a honeybee repellent disclosedherein binds to a honeybee OBP with binding affinity having anassociation rate constant between 1×10⁵ M⁻¹ s⁻¹ to 1×10⁸ M⁻¹ s⁻¹, 1×10⁶M⁻¹ s⁻¹ to 1×10⁸ M⁻¹ s⁻¹, 1×10 M⁻¹ s⁻¹ to 1×10⁷ M⁻¹ s⁻¹, or 1×10⁶ M⁻¹s⁻¹ to 1×10⁷ M⁻¹ s⁻¹.

In another embodiment, a honeybee repellent disclosed herein binds to ahoneybee OBP with binding affinity having a disassociation rate constantof less than 1×10⁻³ s⁻¹, less than 1×10⁻⁴ s⁻¹, or less than 1×10⁻⁵ s⁻¹.In another embodiment, a honeybee repellent disclosed herein binds to ahoneybee OBP with binding affinity having a disassociation rate constantof, e.g., less than 1.0×10⁻⁴ s⁻¹, less than 2.0×10⁻⁴ s⁻¹, less than3.0×10⁻⁴ s⁻¹, less than 4.0×10⁻⁴ s⁻¹, less than 5.0×10⁻⁴ s⁻¹, less than6.0×10⁻⁴ s⁻¹, less than 7.0×10⁻⁴ s⁻¹, less than 8.0×10⁻⁴ s⁻¹, or lessthan 9.0×10⁻⁴ s⁻¹. In another embodiment, a honeybee repellent disclosedherein binds to a honeybee OBP with binding affinity having adisassociation rate constant of, e.g., more than 1×10⁻³ s⁻¹, more than1×10⁻⁴ s⁻¹, or more than 1×10⁻⁵ s⁻¹. In another embodiment, a honeybeerepellent disclosed herein binds to a honeybee OBP with binding affinityhaving a disassociation rate constant of, e.g., more than 1.0×10⁻⁴ s⁻¹,more than 2.0×10⁻⁴ s⁻¹, more than 3.0×10⁻⁴ s⁻¹, more than 4.0×10⁻⁴ s⁻¹,more than 5.0×10⁻⁴ s⁻¹, more than 6.0×10⁻⁴ s⁻¹, more than 7.0×10⁻⁴ s⁻¹,more than 8.0×10⁻⁴ s⁻¹, or more than 9.0×10⁻⁴ s⁻¹.

In another embodiment, a honeybee repellent disclosed herein binds to ahoneybee OBP with binding affinity having an equilibrium disassociationconstant of less than 0.500 nM. In aspects of this embodiment, ahoneybee repellent disclosed herein binds to a honeybee OBP with bindingaffinity having an equilibrium disassociation constant of, e.g., lessthan 0.500 nM, less than 0.450 nM, less than 0.400 nM, less than 0.350nM, less than 0.300 nM, less than 0.250 nM, less than 0.200 nM, lessthan 0.150 nM, less than 0.100 nM, or less than 0.050 nM. In anotherembodiment, a honeybee repellent disclosed herein binds to a honeybeeOBP with binding affinity having an equilibrium disassociation constantof more than 0.500 nM. In aspects of this embodiment, a honeybeerepellent disclosed herein binds to a honeybee OBP with binding affinityhaving an equilibrium disassociation constant of, e.g., more than 0.500nM, more than 0.450 nM, more than 0.400 nM, more than 0.350 nM, morethan 0.300 nM, more than 0.250 nM, more than 0.200 nM, more than 0.150nM, more than 0.100 nM, or more than 0.050 nM.

In another embodiment, a honeybee repellent disclosed herein has abinding affinity that is substantially the same as the binding affinityof 2-heptanone for that honeybee OBP. In aspects of this embodiment, ahoneybee repellent disclosed herein has a binding affinity for ahoneybee OBP that is, e.g., about 75%, about 80%, about 85%, about 90%,about 95%, about 97%, or about 100% that of the binding affinity of2-heptanone for that honeybee OBP. In other aspects of this embodiment,a honeybee repellent disclosed herein has a binding affinity for ahoneybee OBP that is, e.g., at least 75%, at least 80%, at least 85%, atleast 90%, at least 95%, or at least 97% that of the binding affinity of2-heptanone for that honeybee OBP. In other aspects of this embodiment,a honeybee repellent disclosed herein has a binding affinity for ahoneybee OBP that is between, e.g., about 75% to about 97%, about 80% toabout 97%, about 85% to about 97%, about 90% to about 97%, about 75% toabout 100%, about 80% to about 100%, about 85% to about 100%, or about90% to about 100% that of the binding affinity of (R)-(+)-Limonene forthat honeybee OBP.

In an embodiment, the binding affinity of a honeybee repellent thatbinds to a honeybee OBP has a dissociation equilibrium constant that isgreater than the dissociation equilibrium constant of 2-heptanone forthat honeybee OBP by, e.g., at least one-fold, at least two-fold, atleast three-fold, at least four fold, at least five-fold, at leastsix-fold, at least seven-fold, at least eight-fold, at least nine-fold,at least 10-fold, at least 20-fold, at least 30-fold, at least 40-fold,at least 50-fold, at least 60-fold, at least 70-fold, at least 80-fold,at least 90-fold, at least 100-fold, at least 125-fold, at least150-fold, at least 175-fold, or at least 200-fold.

Unless otherwise indicated, when a compound or chemical structuralfeature, such as aryl, phenyl, or a compound named or depicted herein,is referred to as being “optionally substituted,” it includes a featurethat has no substituents (i.e. be unsubstituted), or a feature that is“substituted,” meaning that the feature has one or more substituents.The term “substituent” has the broadest meaning known to one of ordinaryskill in the art, and includes a moiety that replaces one or morehydrogen atoms attached to a parent compound or structural feature. Insome embodiments, the substituent may be an ordinary organic moietyknown in the art, which may have a molecular weight (e.g. the sum of theatomic masses of the atoms of the substituent) of 15 g/mol to 50 g/mol,15 g/mol to 100 g/mol, 15 g/mol to 150 g/mol, 15 g/mol to 200 g/mol, 15g/mol to 300 g/mol, or 15 g/mol to 500 g/mol. In some embodiments, thesubstituent comprises: 0-30, 0-20, 0-10, or 0-5 carbon atoms; and 0-30,0-20, 0-10, or 0-5 heteroatoms independently selected from: N, O, S, Si,F, Cl, Br, or I; provided that the substituent comprises at least oneatom selected from: C, N, O, S, Si, F, Cl, Br, or I. Examples ofsubstituents include, but are not limited to, alkyl, alkenyl, alkynyl,heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, hydroxy,alkoxy, aryloxy, acyl, acyloxy, alkylcarboxylate, thiol, alkylthio,cyano, halo, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl,N-thiocarbamyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido,isocyanato, thiocyanato, isothiocyanato, nitro, silyl, sulfenyl,sulfinyl, sulfonyl, haloalkyl, haloalkoxyl, trihalomethanesulfonyl,trihalomethanesulfonamido, amino, etc.

In some embodiments, any substituent may independently be C₁₋₅ alkyl,such as CH₃, C₂H₅, C₃H₇, C₄H₉, C₅H₁₁, cyclopropyl, cyclobutyl,cyclopentyl, etc.; C₁₋₄—O-alkyl, such as —O—CH₃, —O—C₂H₅, —O—C₃H₇,—O-cyclopropyl, etc.; C₂₋₄ alkenyl, such as —CH₂—CH═CH₂; —O—CH₂CH═CH₂;ester functional groups, such as C₁₋₄—CO₂-alkyl (e.g. —CO₂CH₃, —CO₂C₂H₅,—CO₂C₃H₇, etc.), C₁₋₄ acyloxy, (e.g. —OCOCH₃, —OCOC₂H₅, —OCOC₃H₇, etc.),—CO₂—CF₃, etc.; halo, such as F, Cl, Br, I, etc.; NO₂; ═O; ═S; —OH;amino, such as C₁₋₁₂ amino including NH₂, NHCH₃, N(CH₃)₂, N(C₂H₅)₂,NH(C₃H₇), etc.; amide functional groups, such as C₁₋₁₂ amide groupsincluding —CONH₂, CONH(CH₃), CON(CH₃)₂, CON(C₂H₅)₂, —NCOC₄H₉, etc.;—C═N—OH; —C═N—CH₃; C₁₋₄ acyl, such as COH, COCH₃, COC₂H₅, etc.; COCF₃;—NCOC₄H₉; or two substituents may together be —CH₂—, —C₂H₄—, —C₃H₆—,—O—CH₂—, —O—C₂H₄—, —O—C₃H₆—, —CH₂—O—, —C₂H₄—O—, —C₃H₆—O—, —O—CH₂—O—,—O—C₂H₄—O—, or —O—C₃H₆—O—.

For convenience, the term “molecular weight” is used with respect to amoiety or part of a molecule to indicate the sum of the atomic masses ofthe atoms in the moiety or part of a molecule, even though it may not bea complete molecule.

As used herein the term “alkyl” has the broadest meaning generallyunderstood in the art, and may include a moiety composed of carbon andhydrogen containing no double or triple bonds. Alkyl may be linearalkyl, branched alkyl, cycloalkyl, or a combination thereof, and in someembodiments, may contain from one to thirty-five carbon atoms. In someembodiments, alkyl may include C₁₋₁₀ linear alkyl, such as methyl(—CH₃), ethyl (—CH₂CH₃), n-propyl (—CH₂CH₂CH₃), n-butyl (—CH₂CH₂CH₂CH₃),n-pentyl (—CH₂CH₂CH₂CH₂CH₃), n-hexyl (—CH₂CH₂CH₂CH₂CH₂CH₃), etc.; C₃-10branched alkyl, such as C₃H₇ (e.g. iso-propyl), C₄H₉ (e.g. branchedbutyl isomers), C₅H₁₁ (e.g. branched pentyl isomers), C₆H₁₃ (e.g.branched hexyl isomers), C₇H₁₅ (e.g. heptyl isomers), etc.; C₃₋₁₀cycloalkyl, such as C₃H₅ (e.g. cyclopropyl), C₄H₇ (e.g. cyclobutylisomers such as cyclobutyl, methylcyclopropyl, etc.), C₅H₉ (e.g.cyclopentyl isomers such as cyclopentyl, methylcyclobutyl,dimethylcyclopropyl, etc.) C₆H₁₁ (e.g. cyclohexyl isomers), C₇H₁₃ (e.g.cycloheptyl isomers), etc.; and the like.

Unless otherwise indicated, any reference to a compound herein bystructure, name, or any other means, includes pharmaceuticallyacceptable salts, such as sodium, potassium, and ammonium salts;alternate solid forms, such as polymorphs, solvates, hydrates, etc.;tautomers; or any other chemical species that may rapidly convert to acompound described herein under conditions in which the compounds areused as described herein.

Thus, in one embodiment, a honeybee repellent is a compound having astructure of formula I

wherein X¹ and X² are each independently selected from CH, N and O; R¹and R² are each independently selected from H, C₁₋₆ alkyl, C₂₋₆ alkenyl,C₂₋₆ alkynyl, optionally substituted aryl, optionally substitutedalkylaryl, optionally substituted arylalkyl, alkoxy, optionallysubstituted aryloxy, optionally substituted arylalkoxy, optionallysubstituted alkoxyalkylaryl, alkylamino, aminoalkyl, dialkylamino,optionally substituted arylamino, optionally substituted aminoaryl,heteroalkyl, optionally substituted heteroaryl, optionally substitutedheteroarylalkyl, optionally substituted cyclic heteroalkyl, optionallysubstituted cyclic heteroalkylalkyl, acyl, NH₂, NR⁵R⁶, OH, OR⁵, CN, NO₂,OCF₃, CF₃, Br, Cl, F, 1-amidino, 2-amidino, alkylcarbonyl, morpholino,piperidinyl, dioxanyl, pyranyl, heteroaryl, furanyl, thiophenyl,tetrazole, thiazole, isothiazole, imidazole, thiadiazole, thiadiazoleS-oxide, thiadiazole S,S-dioxide, sulfonylamidine, sulfonylguanidine,sulfamoylamidine, sulfamoylguanidine, pyrazole, oxazole, isoxazole,pyridinyl, pyrimidinyl, piperazine, quinoline, or isoquinoline, with theproviso that if X¹ is O, then R¹ is not present, or if X² is O, then R²is not present

In an aspect of this embodiment, a compound of formula I disclosedherein has a structure of formula Ia

wherein R³ and R⁴ are each independently H, C₁₋₆ alkyl, OC₁₋₆ alkyl,CO₂C₁₋₆ alkyl, phenoxymethanol, halogen, NO₂, SO₂ or when two of R³ orR⁴ are taken together form a cyclic group including, but not limited to,methylene dioxo, benzo, morpholino, piperidinyl, dioxanyl, pyranyl,optionally substituted heteroaryl, furanyl, thiophene, pyrrole,thiazole, isothiazole, imidazole, oxazole, isoxazole, pyridinyl,pyrimidinyl or piperazine; m is 0, 1 or 2; n is 0, 1 or 2; p is 0 to 5;and q is 0 to 5.

In another aspect of this embodiment, a compound of formula I disclosedherein is

In another embodiment, a honeybee repellent is a compound having astructure of formula II

wherein X is O or S; Y is H, C₁₋₆ alkyl, optionally substituted aryl,═O, or ═S; Z¹, Z², and Z³ are each independently selected from N, NH, C,CH, CH₂, O, or S; each R¹ is independently selected from H, C₁₋₆ alkyl,C₂₋₆ alkenyl, C₂₋₆ alkynyl, optionally substituted benzylidine,optionally substituted alkylaryl, optionally substituted arylalkyl,alkoxy, optionally substituted aryloxy, optionally substitutedarylalkoxy, optionally substituted alkoxyalkylaryl optionallysubstituted alkoxyalkylaryl, alkylamino, aminoalkyl, dialkylamino,optionally substituted arylamino, optionally substituted aminoaryl,heteroalkyl, optionally substituted heteroaryl, optionally substitutedheteroarylalkyl, cyclic heteroalkyl, cyclic heteroalkylalkyl, acyl, NH₂,NR⁵R⁶, OH, OR⁵, CN, NO₂, OCF₃, CF₃, Br, Cl, F, 1-amidino, 2-amidino,alkylcarbonyl, morpholino, piperidinyl, dioxanyl, pyranyl, heteroaryl,furanyl, thiophenyl, tetrazole, thiazole, isothiazole, imidazole,thiadiazole, thiadiazole S-oxide, thiadiazole S,S-dioxide,sulfonylamidine, sulfonylguanidine, sulfamoylamidine,sulfamoylguanidine, pyrazole, oxazole, isoxazole, pyridinyl,pyrimidinyl, piperazine, quinoline, isoquinoline or when two of R¹ aretaken together form an optionally substituted cyclic group including,but not limited to, methylene dioxo, benzo, morpholino, piperidinyl,dioxanyl, pyranyl, heteroaryl, furanyl, thiophene, pyrrole, thiazole,isothiazole, imidazole, oxazole, isoxazole, pyridinyl, pyrimidinyl orpiperazine; if Z¹ is O or S, then R² is absent, otherwise R² is H, OH,C₁₋₆ alkyl, optionally substituted aryl; a dashed line represents thepresence or absence of a double bond; and m is 0 to 2.

In an aspect of this embodiment, a compound of formula II disclosedherein has a structure of formula IIa

wherein R² is independently H, OH, C₁₋₆ alkyl, OC₁₋₆ alkyl, CO₂C₁₋₆alkyl, halogen, NO₂, or SO₂; and p is 0 to 8.

In another aspect of this embodiment, a compound of formula II orformula IIa disclosed herein is

In yet another aspect of this embodiment, a compound of formula IIdisclosed herein has a structure of formula IIb

wherein each R³ is independently H, OH, C₁₋₆ alkyl, OC₁₋₆ alkyl, CO₂C₁₋₆alkyl, halogen, NO₂, or SO₂; and q is 0 to 5.

In yet another aspect of this embodiment, a compound of formula II orformula IIb disclosed herein is

In still another aspect of this embodiment, a compound of formula IIdisclosed herein has a structure of formula IIc

wherein R⁴ and R⁵ are each independently H, OH, C₁₋₆ alkyl, OC₁₋₆ alkyl,CO₂C₁₋₆ alkyl, halogen, NO₂, or SO₂; Z⁴ is O, NH, or S; r is 0 to 5; ands is 0 to 3.

In still another aspect of this embodiment, a compound of formula II orformula IIc disclosed herein is

In yet another aspect of this embodiment, a compound of formula IIdisclosed herein has a structure of formula IId

wherein R⁶ and R⁷ are each independently H, OH, C₁₋₆ alkyl, OC₁₋₆ alkyl,CO₂C₁₋₆ alkyl, halogen, NO₂, or SO₂; t is 0 to 5; and u is 0 to 5.

In yet another aspect of this embodiment, a compound of formula II orformula IId disclosed herein is

In yet another embodiment, a honeybee repellent is a compound having astructure of formula III

wherein X¹ is O, N or S; R¹ and R² are each independently selected fromH, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, optionally substituted aryl,optionally substituted alkylaryl, optionally substituted arylalkyl,alkoxy, optionally substituted aryloxy, optionally substitutedarylalkoxy, optionally substituted alkoxyalkylaryl optionallysubstituted alkoxyalkylaryl, alkylamino, aminoalkyl, dialkylamino,optionally substituted arylamino, optionally substituted aminoaryl,heteroalkyl, optionally substituted heteroaryl, optionally substitutedheteroarylalkyl, cyclic heteroalkyl, cyclic heteroalkylalkyl, acyl, NH₂,NR⁵R⁶, OH, OR⁵, CN, NO₂, OCF₃, CF₃, Br, Cl, F, 1-amidino, 2-amidino,alkylcarbonyl, morpholino, piperidinyl, dioxanyl, pyranyl, heteroaryl,furanyl, thiophenyl, tetrazole, thiazole, isothiazole, imidazole,thiadiazole, thiadiazole S-oxide, thiadiazole S,S-dioxide,sulfonylamidine, sulfonylguanidine, sulfamoylamidine,sulfamoylguanidine, pyrazole, oxazole, isoxazole, pyridinyl,pyrimidinyl, piperazine, quinoline, or isoquinoline; m is 0 to 5; and nis 0 to 5.

In an aspect of this embodiment, a compound of formula III disclosedherein is

In still another embodiment, a honeybee repellent is a compound having astructure of formula IV

wherein X² is O, N or S; R³ and R⁴ are each independently selected fromH, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, optionally substitutedalkylaryl, optionally substituted arylalkyl, alkoxy, optionallysubstituted aryloxy, optionally substituted arylalkoxy, optionallysubstituted alkoxyalkylaryl optionally substituted alkoxyalkylaryl,alkylamino, aminoalkyl, dialkylamino, optionally substituted arylamino,optionally substituted aminoaryl, heteroalkyl, optionally substitutedheteroaryl, optionally substituted heteroarylalkyl, cyclic heteroalkyl,cyclic heteroalkylalkyl, acyl, NH₂, NR⁵R⁶, OH, OR⁵, CN, NO₂, C═N—OH,OCF₃, CF₃, Br, Cl, F, 1-amidino, 2-amidino, alkylcarbonyl, morpholino,piperidinyl, dioxanyl, pyranyl, heteroaryl, furanyl, thiophenyl,tetrazole, thiazole, isothiazole, imidazole, thiadiazole, thiadiazoleS-oxide, thiadiazole S,S-dioxide, sulfonylamidine, sulfonylguanidine,sulfamoylamidine, sulfamoylguanidine, pyrazole, oxazole, isoxazole,pyridinyl, pyrimidinyl, piperazine, quinoline, or isoquinoline; o is 0to 5; and p is 0 to 5.

In an aspect of this embodiment, a compound of formula IV disclosedherein is

In a further embodiment, a honeybee repellent is a compound having astructure of formula V

wherein X³ is O, NH or S; A¹ and A² are each independently selected fromoptionally substituted phenyl, optionally substituted morpholino,optionally substituted piperidinyl, optionally substituted dioxanyl,optionally substituted pyranyl, optionally substituted heteroaryl,optionally substituted furanyl, optionally substituted thiophenyl,optionally substituted tetrazole, optionally substituted thiazole,optionally substituted isothiazole, optionally substituted imidazole,optionally substituted thiadiazole, optionally substituted thiadiazoleS-oxide, optionally substituted thiadiazole optionally substitutedS,S-dioxide, optionally substituted sulfonylamidine, optionallysubstituted sulfonylguanidine, optionally substituted sulfamoylamidine,optionally substituted sulfamoylguanidine, optionally substitutedpyrazole, optionally substituted oxazole, optionally substitutedisoxazole, optionally substituted pyridinyl, optionally substitutedpyrimidinyl, optionally substituted piperazine, optionally substitutedquinoline, optionally substituted dihydroquinoline, and optionallysubstituted isoquinoline; and r is 0 to 5.

In an aspect of this embodiment, a compound of formula II disclosedherein has a structure of formula Va

wherein a dotted line represent the presence or absence of a doublebond; R⁵ and R⁶ are each independently selected from H, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, ═S, ═O, optionally substituted alkylaryl,optionally substituted arylalkyl, alkoxy, optionally substitutedaryloxy, optionally substituted arylalkoxy, optionally substitutedalkoxyalkylaryl optionally substituted alkoxyalkylaryl, alkylamino,aminoalkyl, dialkylamino, optionally substituted arylamino, optionallysubstituted aminoaryl, heteroalkyl, optionally substituted heteroaryl,optionally substituted heteroarylalkyl, cyclic heteroalkyl, cyclicheteroalkylalkyl, acyl, NH₂, NR⁵R⁶, OH, OR⁵, CN, NO₂, OCF₃, CF₃, Br, Cl,F, 1-amidino, 2-amidino; s is 0 to 9; and t is 0 to 5.

In an aspect of this embodiment, a compound of formula V or formula Vadisclosed herein is

In another embodiment, a honeybee repellent is a compound having astructure of formula VI

wherein R⁷, R⁸ and R⁹ are each independently selected from H, C₁₋₆alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, ═S, ═O, optionally substitutedalkylaryl, optionally substituted arylalkyl, alkoxy, optionallysubstituted aryloxy, optionally substituted arylalkoxy, optionallysubstituted alkoxyalkylaryl, alkylamino, aminoalkyl, dialkylamino,optionally substituted arylamino, optionally substituted aminoaryl,heteroalkyl, optionally substituted heteroaryl, optionally substitutedheteroarylalkyl, cyclic heteroalkyl, cyclic heteroalkylalkyl, acyl, NH₂,NR⁵R⁶, OH, OR⁵, CN, NO₂, OCF₃, CF₃, Br, Cl, F, 1-amidino, 2-amidino; uis 0 to 5; v is 0 to 5; and w is 0 to 5.

In an aspect of this embodiment, a compound of formula VI disclosedherein is

In yet another embodiment, a honeybee repellent is a compound having astructure of formula VII

wherein each R¹⁰ is independently selected from H, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, ═S, ═O, optionally substituted phenyl, optionallysubstituted alkylaryl, optionally substituted arylalkyl, alkoxy,optionally substituted aryloxy, optionally substituted arylalkoxy,optionally substituted alkoxyalkylaryl, alkylamino, aminoalkyl,dialkylamino, optionally substituted arylamino, optionally substitutedaminoaryl, heteroalkyl, optionally substituted heteroaryl, optionallysubstituted heteroarylalkyl, cyclic heteroalkyl, cyclicheteroalkylalkyl, acyl, NH₂, NR⁵R⁶, OH, OR⁵, CN, NO₂, OCF₃, CF₃, Br, Cl,F, 1-amidino, 2-amidino; and x is 0 to 9.

In an aspect of this embodiment, a compound of formula VII disclosedherein is

In still another embodiment, a honeybee repellent is a compound having astructure of formula VIII

wherein R¹¹ and R¹² are each independently selected from H, C₁₋₆ alkyl,C₂₋₆ alkenyl, C₂₋₆ alkynyl, ═S, ═O, optionally substituted alkylaryl,optionally substituted arylalkyl, alkoxy, optionally substitutedaryloxy, optionally substituted arylalkoxy, optionally substitutedalkoxyalkylaryl, alkylamino, aminoalkyl, dialkylamino, optionallysubstituted arylamino, optionally substituted aminoaryl, heteroalkyl,optionally substituted heteroaryl, optionally substitutedheteroarylalkyl, cyclic heteroalkyl, cyclic heteroalkylalkyl, acyl, NH₂,NR⁵R⁶, OH, OR⁵, CN, NO₂, OCF₃, CF₃, Br, Cl, F, 1-amidino, 2-amidino; thedashed line represents the presence or absence of a double bond; y is 0to 9; and z is 0 to 5.

In an aspect of this embodiment, a compound of formula VIII disclosedherein is

In a further embodiment, a honeybee repellent is a compound having astructure of formula IX

wherein R is H, OH, halogen, C₁₋₆ alkyl; R¹³ and R¹⁴ are eachindependently selected from H, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,═S, ═O, optionally substituted alkylaryl, optionally substitutedarylalkyl, alkoxy, optionally substituted aryloxy, optionallysubstituted arylalkoxy, optionally substituted alkoxyalkylaryl,alkylamino, aminoalkyl, dialkylamino, optionally substituted arylamino,optionally substituted aminoaryl, heteroalkyl, optionally substitutedheteroaryl, optionally substituted heteroarylalkyl, cyclic heteroalkyl,cyclic heteroalkylalkyl, acyl, NH₂, NR⁵R⁶, OH, OR⁵, CN, NO₂, OCF₃, CF₃,Br, Cl, F, 1-amidino, 2-amidino; Y¹ and Y² are each independentlyselected from O, S, NH, or CH₂; Z is O or S; a is 0 to 5; and b is 0 to9.

In an aspect of this embodiment, a compound of formula IX disclosedherein is

In another embodiment, a honeybee repellent is a compound having astructure of formula X

wherein each R¹⁵ is independently selected from H, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, ═S, ═O, optionally substituted alkylaryl,optionally substituted arylalkyl, alkoxy, optionally substitutedaryloxy, optionally substituted arylalkoxy, optionally substitutedalkoxyalkylaryl, alkylamino, aminoalkyl, dialkylamino, optionallysubstituted arylamino, optionally substituted aminoaryl, heteroalkyl,optionally substituted heteroaryl, optionally substitutedheteroarylalkyl, cyclic heteroalkyl, cyclic heteroalkylalkyl, acyl, NH₂,NR⁵R⁶, OH, OR⁵, CN, NO₂, OCF₃, CF₃, Br, Cl, F, 1-amidino, 2-amidino; andc is 0 to 5.

In an aspect of this embodiment, a compound of formula X disclosedherein is

In yet another embodiment, a honeybee repellent is a compound having astructure of formula XI

wherein each R¹⁶ is independently selected from H, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, ═S, ═O, optionally substituted alkylaryl,optionally substituted arylalkyl, alkoxy, optionally substitutedaryloxy, optionally substituted arylalkoxy, optionally substitutedalkoxyalkylaryl, alkylamino, aminoalkyl, dialkylamino, optionallysubstituted arylamino, optionally substituted aminoaryl, heteroalkyl,optionally substituted heteroaryl, optionally substitutedheteroarylalkyl, cyclic heteroalkyl, cyclic heteroalkylalkyl, acyl, NH₂,NR⁵R⁶, OH, OR⁵, CN, NO₂, OCF₃, CF₃, Br, Cl, F, 1-amidino, 2-amidino; andd is 0 to 9.

In an aspect of this embodiment, a compound of formula XI disclosedherein is

In yet another embodiment, a honeybee repellent is a compound having astructure of formula XII

wherein R¹⁷ and R¹⁸ are each independently selected from H, C₁₋₆ alkyl,C₂₋₆ alkenyl, C₂₋₆ alkynyl, ═S, ═O, optionally substituted alkylaryl,optionally substituted arylalkyl, alkoxy, optionally substitutedaryloxy, optionally substituted arylalkoxy, optionally substitutedalkoxyalkylaryl, alkylamino, aminoalkyl, dialkylamino, optionallysubstituted arylamino, optionally substituted aminoaryl, heteroalkyl,optionally substituted heteroaryl, optionally substitutedheteroarylalkyl, cyclic heteroalkyl, cyclic heteroalkylalkyl, acyl, NH₂,NR⁵R⁶, OH, OR⁵, CN, NO₂, OCF₃, CF₃, Br, Cl, F, 1-amidino, 2-amidino; adashed line represent the presence or absence of a double bond; e is 0to 5; and f is 0 to 5.

In an aspect of this embodiment, a compound of formula XII disclosedherein is

In still another embodiment, a honeybee repellent is a compound having astructure of formula XIII

wherein X¹ and X² are each independently selected from O, N or S; andR¹, R², R³, and R⁴ are each independently selected from H, C₁₋₆ alkyl,C₂₋₆ alkenyl, C₂₋₆ alkynyl, optionally substituted alkylaryl, optionallysubstituted arylalkyl, alkoxy, optionally substituted aryloxy,optionally substituted arylalkoxy, optionally substitutedalkoxyalkylaryl, alkylamino, aminoalkyl, dialkylamino, optionallysubstituted arylamino, optionally substituted aminoaryl, heteroalkyl,optionally substituted heteroaryl, optionally substitutedheteroarylalkyl, cyclic heteroalkyl, cyclic heteroalkylalkyl, acyl,optionally substituted benzoyl, optionally substituted 2-benzoylethenyl,NH₂, NR⁵R⁶, OH, OR⁵, CN, NO₂, OCF₃, CF₃, Br, Cl, F, 1-amidino,2-amidino, alkylcarbonyl, morpholino, piperidinyl, dioxanyl, pyranyl,optionally substituted heteroaryl, furanyl, thiophenyl, tetrazole,thiazole, isothiazole, imidazole, thiadiazole, thiadiazole S-oxide,thiadiazole S,S-dioxide, sulfonylamidine, sulfonylguanidine,sulfamoylamidine, sulfamoylguanidine, pyrazole, oxazole, isoxazole,pyridinyl, pyrimidinyl, piperazine, quinoline, isoquinoline or when R³and R⁴ are taken together form a cyclic group including, but not limitedto, methylene dioxo, benzo, morpholino, piperidinyl, dioxanyl, pyranyl,heteroaryl, furanyl, thiophene, pyrrole, thiazole, isothiazole,imidazole, oxazole, isoxazole, pyridinyl, pyrimidinyl or piperazine andsubstituted derivatives thereof.

In an aspect of this embodiment, a compound of formula XIII disclosedherein has a structure of formula XIIIa

wherein each R⁵ is independently H, OH, C₁₋₆ alkyl, OC₁₋₆ alkyl, CO₂C₁₋₆alkyl, halogen, NO₂, or SO₂; Z is C or N; and m is 0 to 5.

In an aspect of this embodiment, a compound of formula XIII or formulaXIIIa disclosed herein is

In an aspect of this embodiment, a compound of formula XIII disclosedherein has a structure of formula XIIIb

wherein R⁶ and R⁷ are each independently H, OH, C₁₋₆ alkyl, OC₁₋₆ alkyl,CO₂C₁₋₆ alkyl, halogen, NO₂, or SO₂; n is 0 to 5; and o is 0 to 5.

In an aspect of this embodiment, a compound of formula XIII or formulaXIIIb disclosed herein is

In some embodiments, a honeybee repellent may be optionally substituted1-benzyl-4-(4-methoxy-2,3-dimethylbenzyl) piperazine. In someembodiments, a honeybee repellent may be optionally substituted1-[(6-nitro-1,3-benzodioxol-5-yl)methyl]-4-phenylpiperazine. In someembodiments, a honeybee repellent may be optionally substituted4-[4-nitro-3-(2-phenoxyethoxy)phenyl]morpholine. In some embodiments, ahoneybee repellent may be optionally substituted1-(3-chlorophenyl)-4-[(6-nitro-1,3-benzodioxol-5-yl)methyl]piperazine.In some embodiments, a honeybee repellent may be optionally substituted1-(4-methoxybenzyl)-4-(3-methylbenzyl)piperazine. In some embodiments, ahoneybee repellent may be optionally substituted4-(4-methoxy-2,3-dimethylbenzyl) morpholine. In some embodiments, ahoneybee repellent may be optionally substituted1-benzyl-4-(4-methoxy-3-methylbenzyl)piperazine. In some embodiments, ahoneybee repellent may be optionally substituted1-(4-methoxy-2,3-dimethylbenzyl)-4-methyl piperazine. In someembodiments, a honeybee repellent may be optionally substituted1-(4-methoxy-2,3-dimethylbenzyl)-4-methylpiperazine. In someembodiments, a honeybee repellent may be optionally substituted1-(1,3-benzodioxol-5-ylmethyl)-4-(4,5-dimethoxy-2-nitrobenzyl)piperazine.In some embodiments, a honeybee repellent may be optionally substituted1-(2,3-dimethylphenyl)-4-(4-methoxy-2,3-dimethylbenzyl)piperazine. Insome embodiments, a honeybee repellent may be optionally substituted1-(4-methoxy-2,3-dimethylbenzyl)-4-phenylpiperazine. In someembodiments, a honeybee repellent may be optionally substituted1-[3-(4-iodophenoxy)propyl]piperidine. In some embodiments, a honeybeerepellent may be optionally substituted1-(4-methoxy-2,3-dimethylbenzyl)-4-(4-methylphenyl) piperazine.

In some embodiments, a honeybee repellent is not1-benzyl-4-(4-methoxy-2,3-dimethylbenzyl) piperazine. In someembodiments, a honeybee repellent is not1-[(6-nitro-1,3-benzodioxol-5-yl)methyl]-4-phenylpiperazine. In someembodiments, a honeybee repellent is not4-[4-nitro-3-(2-phenoxyethoxy)phenyl]morpholine. In some embodiments, ahoneybee repellent is not1-(3-chlorophenyl)-4-[(6-nitro-1,3-benzodioxol-5-yl)methyl]piperazine.In some embodiments, a honeybee repellent is not1-(4-methoxybenzyl)-4-(3-methylbenzyl)piperazine. In some embodiments, ahoneybee repellent is not 4-(4-methoxy-2,3-dimethylbenzyl) morpholine.In some embodiments, a honeybee repellent is not1-benzyl-4-(4-methoxy-3-methylbenzyl)piperazine. In some embodiments, ahoneybee repellent is not 1-(4-methoxy-2,3-dimethylbenzyl)-4-methylpiperazine. In some embodiments, a honeybee repellent is not1-(4-methoxy-2,3-dimethylbenzyl)-4-methylpiperazine. In someembodiments, a honeybee repellent is not1-(1,3-benzodioxol-5-ylmethyl)-4-(4,5-dimethoxy-2-nitrobenzyl)piperazine.In some embodiments, a honeybee repellent is not1-(2,3-dimethylphenyl)-4-(4-methoxy-2,3-dimethylbenzyl)piperazine. Insome embodiments, a honeybee repellent is not1-(4-methoxy-2,3-dimethylbenzyl)-4-phenylpiperazine. In someembodiments, a honeybee repellent is not1-[3-(4-iodophenoxy)propyl]piperidine. In some embodiments, a honeybeerepellent is not1-(4-methoxy-2,3-dimethylbenzyl)-4-(4-methylphenyl)piperazine.

In some embodiments, a honeybee repellent may be optionally substituted2-{[(2-methoxy-1-naphthyl)methylene]amino}-1H-isoindole-1,3(2H)-dione.In some embodiments, a honeybee repellent may be optionally substituted2-[(2-ethoxybenzylidene)amino]-1H-isoindole-1,3(2H)-dione. In someembodiments, a honeybee repellent may be optionally substituted3-ethyl-5-(4-hydroxybenzylidene)-2-thioxo-1,3-thiazolidin-4-one. In someembodiments, a honeybee repellent may be optionally substituted3-butyl-5-(3-hydroxybenzylidene)-2-thioxo-1,3-thiazolidin-4-one. In someembodiments, a honeybee repellent may be optionally substituted5-(3-bromo-4-methoxybenzylidene)-3-methyl-2-thioxo-1,3-thiazolidin-4-one.In some embodiments, a honeybee repellent may be optionally substituted5-(5-bromo-2-hydroxybenzylidene)-3-ethyl-2-thioxo-1,3-thiazolidin-4-one.In some embodiments, a honeybee repellent may be optionally substituted2-phenyl-4-(2-thienylmethylene)-1,3-oxazol-5(4H)-one. In someembodiments, a honeybee repellent may be optionally substituted5-(4-chlorobenzylidene)-3-(2-methoxyphenyl)-2-thioxo-1,3-thiazolidin-4-one.In some embodiments, a honeybee repellent may be optionally substituted3-(4-bromophenyl)-5-(4-hydroxybenzylidene)-2-thioxo-1,3-thiazolidin-4-one.In some embodiments, a honeybee repellent may be optionally substituted4-[3-bromo-4-(dimethylamino)benzylidene]-2-(2-methoxyphenyl)-1,3-oxazol-5(4H)-one.

In some embodiments, a honeybee repellent is not2-{[(2-methoxy-1-naphthyl)methylene]amino}-1H-isoindole-1,3(2H)-dione.In some embodiments, a honeybee repellent is not2-[(2-ethoxybenzylidene)amino]-1H-isoindole-1,3(2H)-dione. In someembodiments, a honeybee repellent is not3-ethyl-5-(4-hydroxybenzylidene)-2-thioxo-1,3-thiazolidin-4-one. In someembodiments, a honeybee repellent is not3-butyl-5-(3-hydroxybenzylidene)-2-thioxo-1,3-thiazolidin-4-one. In someembodiments, a honeybee repellent is not5-(3-bromo-4-methoxybenzylidene)-3-methyl-2-thioxo-1,3-thiazolidin-4-one.In some embodiments, a honeybee repellent is not5-(5-bromo-2-hydroxybenzylidene)-3-ethyl-2-thioxo-1,3-thiazolidin-4-one.In some embodiments, a honeybee repellent is not2-phenyl-4-(2-thienylmethylene)-1,3-oxazol-5(4H)-one. In someembodiments, a honeybee repellent is not5-(4-chlorobenzylidene)-3-(2-methoxyphenyl)-2-thioxo-1,3-thiazolidin-4-one.In some embodiments, a honeybee repellent is not3-(4-bromophenyl)-5-(4-hydroxybenzylidene)-2-thioxo-1,3-thiazolidin-4-one.In some embodiments, a honeybee repellent is not4-[3-bromo-4-(dimethylamino)benzylidene]-2-(2-methoxyphenyl)-1,3-oxazol-5(4H)-one.

In some embodiments, a honeybee repellent may be optionally substituted4-[2-(4-nitrophenyl)vinyl]phenol. In some embodiments, a honeybeerepellent may be optionally substituted3-{2-[(4-fluorobenzyl)amino]phenyl}-2(1H)-quinoxalinone. In someembodiments, a honeybee repellent may be optionally substituted4-bromo-3-chlorophenyl)(4-ethoxybenzylidene)amine. In some embodiments,a honeybee repellent may be optionally substituted4-[(2-chloro-5-nitrobenzylidene)amino]phenol. In some embodiments, ahoneybee repellent may be optionally substituted2-[(2-hydroxy-3,5-diiodobenzylidene)amino]-4,6-dimethylphenol. In someembodiments, a honeybee repellent may be optionally substituted(2-methoxybenzyl)(4-methoxy-3-biphenylyl)amine. In some embodiments, ahoneybee repellent may be optionally substituted2-{[(5-ethyl-2-hydroxyphenyl)imino]methyl}-4,6-diiodophenol.

In some embodiments, a honeybee repellent is not4-[2-(4-nitrophenyl)vinyl]phenol. In some embodiments, a honeybeerepellent is not3-{2-[(4-fluorobenzyl)amino]phenyl}-2(1H)-quinoxalinone. In someembodiments, a honeybee repellent is not4-bromo-3-chlorophenyl)(4-ethoxybenzylidene)amine. In some embodiments,a honeybee repellent is not4-[(2-chloro-5-nitrobenzylidene)amino]phenol. In some embodiments, ahoneybee repellent is not2-[(2-hydroxy-3,5-diiodobenzylidene)amino]-4,6-dimethylphenol. In someembodiments, a honeybee repellent is not(2-methoxybenzyl)(4-methoxy-3-biphenylyl)amine. In some embodiments, ahoneybee repellent is not2-{[(5-ethyl-2-hydroxyphenyl)imino]methyl}-4,6-diiodophenol.

In some embodiments, a honeybee repellent may be optionally substituted3-methoxy-4-(4-nitrophenoxy)benzaldehyde oxime. In some embodiments, ahoneybee repellent is not 3-methoxy-4-(4-nitrophenoxy)benzaldehydeoxime.

In some embodiments, a honeybee repellent may be optionally substituted1-butyl-4-hydroxy-2-oxo-N-(2-pyridinylmethyl)-1,2-dihydro-3-quinolinecarboxamide.In some embodiments, a honeybee repellent may be optionally substituted2-acetyl-4-chlorophenyl 4-methylbenzoate. In some embodiments, ahoneybee repellent may be optionally substitutedN-(2-fluorobenzyl)-4-hydroxy-2-oxo-1-propyl-1,2-dihydro-3-quinolinecarboxamide.In some embodiments, a honeybee repellent may be optionally substitutedethyl 2-(benzoylamino)-5-ethyl-3-thiophenecarboxylate.

In some embodiments, a honeybee repellent is not1-butyl-4-hydroxy-2-oxo-N-(2-pyridinylmethyl)-1,2-dihydro-3-quinolinecarboxamide.In some embodiments, a honeybee repellent is not 2-acetyl-4-chlorophenyl4-methylbenzoate. In some embodiments, a honeybee repellent is notN-(2-fluorobenzyl)-4-hydroxy-2-oxo-1-propyl-1,2-dihydro-3-quinolinecarboxamide.In some embodiments, a honeybee repellent is not ethyl2-(benzoylamino)-5-ethyl-3-thiophenecarboxylate.

In some embodiments, a honeybee repellent may be optionally substituted2-(benzoylamino)-N-(2-chlorophenyl)benzamide. In some embodiments, ahoneybee repellent is not 2-(benzoylamino)-N-(2-chlorophenyl)benzamide.

In some embodiments, a honeybee repellent may be optionally substitutedethyl 2-(3-aminophenyl)-4-quinolinecarboxylate. In some embodiments, ahoneybee repellent is not ethyl2-(3-aminophenyl)-4-quinolinecarboxylate.

In some embodiments, a honeybee repellent may be optionally substituted1-(4-bromobenzoyl)-2,2,4-trimethyl-1,2-dihydroquinoline. In someembodiments, a honeybee repellent is not1-(4-bromobenzoyl)-2,2,4-trimethyl-1,2-dihydroquinoline.

In some embodiments, a honeybee repellent may be optionally substituteddimethyl2-(1,2,2-trimethyl-3-thioxo-2,3-dihydro-4(1H)-quinolinylidene)-1,3-dithiole-4,5-dicarboxylate.In some embodiments, a honeybee repellent may be optionally substituteddimethyl2-(2,2,7-trimethyl-3-thioxo-2,3-dihydro-4(1H)-quinolinylidene)-1,3-dithiole-4,5-dicarboxylate.

In some embodiments, a honeybee repellent is not dimethyl2-(1,2,2-trimethyl-3-thioxo-2,3-dihydro-4(1H)-quinolinylidene)-1,3-dithiole-4,5-dicarboxylate.In some embodiments, a honeybee repellent is not dimethyl2-(2,2,7-trimethyl-3-thioxo-2,3-dihydro-4(1H)-quinolinylidene)-1,3-dithiole-4,5-dicarboxylate.

In some embodiments, a honeybee repellent may be optionally substitutedN-(4-methoxy-2,3-dimethylbenzyl)-N,N′,N′-trimethyl-1,2-ethanediamine. Insome embodiments, a honeybee repellent is notN-(4-methoxy-2,3-dimethylbenzyl)-N, N′,N′-trimethyl-1,2-ethanediamine.

In some embodiments, a honeybee repellent may be optionally substituted1,2,3-trichloro-4-(isopropylamino)anthra-9,10-quinone. In someembodiments, a honeybee repellent is not1,2,3-trichloro-4-(isopropylamino)anthra-9,10-quinone.

In some embodiments, a honeybee repellent may be optionally substituted[1-(3-nitrobenzyl)-3-piperidinyl]methyl 3-phenylacrylate. In someembodiments, a honeybee repellent is not[1-(3-nitrobenzyl)-3-piperidinyl]methyl 3-phenylacrylate.

In some embodiments, a honeybee repellent may be optionally substituted(3-amino-4,6-dimethylthieno[2,3-b]pyridin-2-yl)(4-chlorophenyl)methanone. In some embodiments, a honeybee repellent maybe optionally substituted(4-bromophenyl)(5-methoxy-2-methyl-1-benzofuran-3-yl)methanone. In someembodiments, a honeybee repellent may be optionally substituted1-(4-methoxyphenyl)-3-(2-methyl-1H-indol-3-yl)-2-propen-1-one. In someembodiments, a honeybee repellent may be optionally substituted2-[2-(3,5-dimethyl-1H-pyrazol-1-yl)-6-phenyl-4-pyrimidinyl]phenol.

In some embodiments, a honeybee repellent is not(3-amino-4,6-dimethylthieno[2,3-b]pyridin-2-yl)(4-chlorophenyl)methanone. In some embodiments, a honeybee repellent isnot (4-bromophenyl)(5-methoxy-2-methyl-1-benzofuran-3-yl)methanone. Insome embodiments, a honeybee repellent is not1-(4-methoxyphenyl)-3-(2-methyl-1H-indol-3-yl)-2-propen-1-one. In someembodiments, a honeybee repellent is not2-[2-(3,5-dimethyl-1H-pyrazol-1-yl)-6-phenyl-4-pyrimidinyl]phenol.

Aspects of the present specification provide, in part, a compositioncomprising a honeybee repellent disclosed herein. A compositiondisclosed herein comprises a repellent compound disclosed herein and isuseful in repelling honeybees from an individual and/or a locationtreated with the composition. As such, a composition disclosed herein isuseful for any application that reduces bee-human interaction or abee-location interaction. A composition may be administered to anindividual or location alone, or in combination with other supplementaryactive ingredients, agents, or drugs.

A composition disclosed herein may comprise one or more honeybeerepellents disclosed herein. In one embodiment, a composition disclosedherein may comprise only a single a honeybee repellent disclosed herein.In another embodiment, a composition disclosed herein may comprise aplurality of honeybee repellents disclosed herein. In aspects of thisembodiment, a composition disclosed herein comprises at least twohoneybee repellents, at least three honeybee repellents, at least fourhoneybee repellents, or at least five honeybee repellents. In otheraspects of this embodiment, a composition disclosed herein comprises atmost two honeybee repellents, at most three honeybee repellents, or atmost four honeybee repellents. In yet other aspects of this embodiment,a composition disclosed herein comprises one to three honeybeerepellents, two to four honeybee repellents, two to five honeybeerepellents, three to five honeybee repellents, or two to three honeybeerepellents.

In an embodiment, a composition disclosed herein includes a repellent offormula I, formula II, formula III, formula IV, formula V, formula VI,formula VII, formula VIII, formula IX, formula X, formula XI, formulaXII, formula XIII, or any combination thereof.

In an embodiment, a composition disclosed herein has a honeybeerepellency activity. In aspects of this embodiment, presence of acomposition repels honeybees by, e.g., at least 10%, at least 15%, atleast 20%, at least 25%, at least 30%, at least 35%, at least 40%, atleast 45%, at least 50%, at least 55%, at least 60%, at least 65%, atleast 70%, at least 75%, at least 80%, at least 85%, at least 90%, or atleast 95%, as compared to not having the composition present. In otheraspects of this embodiment, presence of a composition repels honeybeesby, e.g., about 10% to about 100%, about 20% to about 100%, about 30% toabout 100%, about 40% to about 100%, about 50% to about 100%, about 60%to about 100%, about 70% to about 100%, about 80% to about 100%, about10% to about 90%, about 20% to about 90%, about 30% to about 90%, about40% to about 90%, about 50% to about 90%, about 60% to about 90%, about70% to about 90%, about 10% to about 80%, about 20% to about 80%, about30% to about 80%, about 40% to about 80%, about 50% to about 80%, orabout 60% to about 80%, about 10% to about 70%, about 20% to about 70%,about 30% to about 70%, about 40% to about 70%, or about 50% to about70%, as compared to not having the composition present.

In an embodiment, a composition disclosed herein reduces a honeybeeinteraction with a mammal or location. In aspects of this embodiment, acomposition reduces honeybee interaction with a mammal or location by,e.g., at least 10%, at least 15%, at least 20%, at least 25%, at least30%, at least 35%, at least 40%, at least 45%, at least 50%, at least55%, at least 60%, at least 65%, at least 70%, at least 75%, at least80%, at least 85%, at least 90%, or at least 95%. In other aspects ofthis embodiment, a composition reduces honeybee interaction with amammal or location by, e.g., about 10% to about 100%, about 20% to about100%, about 30% to about 100%, about 40% to about 100%, about 50% toabout 100%, about 60% to about 100%, about 70% to about 100%, about 80%to about 100%, about 10% to about 90%, about 20% to about 90%, about 30%to about 90%, about 40% to about 90%, about 50% to about 90%, about 60%to about 90%, about 70% to about 90%, about 10% to about 80%, about 20%to about 80%, about 30% to about 80%, about 40% to about 80%, about 50%to about 80%, or about 60% to about 80%, about 10% to about 70%, about20% to about 70%, about 30% to about 70%, about 40% to about 70%, orabout 50% to about 70%.

In an embodiment, a composition disclosed herein reduces an ability of ahoneybee to obtain a meal from a plant. In aspects of this embodiment, acomposition reduces an ability of a honeybee to obtain a meal from aplant by, e.g., at least 10%, at least 15%, at least 20%, at least 25%,at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, atleast 55%, at least 60%, at least 65%, at least 70%, at least 75%, atleast 80%, at least 85%, at least 90%, or at least 95%. In other aspectsof this embodiment, a composition reduces an ability of a honeybee toobtain a meal from a plant by, e.g., about 10% to about 100%, about 20%to about 100%, about 30% to about 100%, about 40% to about 100%, about50% to about 100%, about 60% to about 100%, about 70% to about 100%,about 80% to about 100%, about 10% to about 90%, about 20% to about 90%,about 30% to about 90%, about 40% to about 90%, about 50% to about 90%,about 60% to about 90%, about 70% to about 90%, about 10% to about 80%,about 20% to about 80%, about 30% to about 80%, about 40% to about 80%,about 50% to about 80%, or about 60% to about 80%, about 10% to about70%, about 20% to about 70%, about 30% to about 70%, about 40% to about70%, or about 50% to about 70%.

A composition disclosed herein can take any of a variety of dosage formsincluding, without limitation, a liquid composition, such as, e.g., asolution, suspension, emulsion; a semi-solid composition, such as, e.g.,a ointment, cream, balm, foam, gel, or salve or a solid composition,such as, e.g., lyophilizate, powder, granule, pellet, capsule; or anyother dosage form suitable for applying a repellent compound disclosedherein to a mammal, plant, and/or location to be treated. In oneembodiment, in liquid, semi-solid, and solid forms, an amount of arepellent compound disclosed herein typically is between about 0.0001%(w/v) to about 50% (w/v), about 0.001% (w/v) to about 10.0% (w/v), orabout 0.01% (w/v) to about 1.0% (w/v). In another aspect embodiment, inliquid, semi-solid, and solid forms, an amount of a repellent compounddisclosed herein typically is between about 0.001 μg/cm² to about 500μg/cm², about 0.01 μg/cm² to about 100 μg/cm², or about 0.1 μg/cm² toabout 10 μg/cm². In another aspect embodiment, in liquid, semi-solid,and solid forms, an amount of a repellent compound disclosed hereintypically is between about 0.01 nmole/cm² to about 1000 nmole/cm², about0.1 nmole/cm² to about 100 nmole/cm², or about 1 nmole/cm² to about 50nmole/cm². In another embodiment, in liquid, semi-solid, and solidforms, an amount of a repellent compound disclosed herein is typicallyis between about 0.001 mg/L to about 500 mg/L, about 0.01 mg/L to about100 mg/L, or about 0.1 mg/L to about 50 mg/L.

The amount of a honeybee repellent disclosed herein used in thecompositions disclosed herein is an effective amount. As used herein,the term “effective amount” refers to an amount of a honeybee repellentor composition disclosed herein sufficient to repel or direct movementof honeybees to the source of repellent compound release.

In aspects of this embodiment, a composition comprises a honeybeerepellent in an effective amount of, e.g., at least 0.0001%, at least0.00025%, at least 0.0005%, at least 0.00075%, at least 0.001%, at least0.0025%, at least 0.005%, at least 0.0075%, at least 0.01%, at least0.025%, at least 0.05%, at least 0.075%, at least 0.1%, at least 0.25%,at least 0.5%, at least 0.75%, at least 1%, at least 2.5%, at least 5%,at least 7.5%, at least 10%, at least 25%, or at least 50%, by weight ofa composition.

In other aspects of this embodiment, a composition comprises a honeybeerepellent in an effective amount of between, e.g., about 0.0001% toabout 0.001%, about 0.0001% to about 0.01%, about 0.0001% to about 0.1%,about 0.00025% to about 0.0025%, about 0.00025% to about 0.025%, about0.00025% to about 0.25%, about 0.0005% to about 0.005%, about 0.0005% toabout 0.05%, about 0.0005% to about 0.75%, about 0.00075% to about0.0075%, about 0.00075% to about 0.075%, about 0.00075% to about 0.75%,about 0.001% to about 0.01%, about 0.001% to about 0.1%, about 0.001% toabout 1%, about 0.0025% to about 0.025%, about 0.0025% to about 0.25%,about 0.0025% to about 2.5%, about 0.005% to about 0.05%, about 0.005%to about 0.5%, about 0.005% to about 5%, about 0.0075% to about 0.075%,about 0.0075% to about 0.75%, about 0.0075% to about 7.5%, about 0.01%to about 0.1%, about 0.01% to about 1%, about 0.01% to about 10%, about0.025% to about 0.25%, about 0.025% to about 2.5%, about 0.025% to about25%, about 0.05% to about 0.5%, about 0.05% to about 5%, about 0.05% toabout 50%, about 0.075% to about 0.75%, about 0.075% to about 7.5%, orabout 0.075% to about 75%, by weight of a composition. In yet otheraspects of this embodiment, a composition comprises a honeybee repellentin an effective amount of between, e.g., about 0.005% to about 0.015%,about 0.0025% to about 0.025%, or about 0.006% to about 0.016%, byweight of a composition.

A composition disclosed herein may optionally comprise one or moreadditional compounds providing an additional beneficial or otherwiseuseful effect. Such compounds include, without limitation, an adhesive,a solvent, a wetting agent, an emulsifying agent, a carrier, a diluent,a dispersing agent an insecticide, a pesticide, a fungicide, afertilizer of a micronutrient or macronutrient nature, a herbicide, afeeding inhibitor, an insect molting inhibitor, an insect matinginhibitor, an insect maturation inhibitor, a nematocide, a nutritionalor horticultural supplement, a larvicide, a seed, or any combinationthereof. Such compounds are known to a person of ordinary skill in theart.

In one aspect of this embodiment, a composition disclosed herein mayoptionally comprise an insecticide. In another aspect of thisembodiment, a composition disclosed herein may optionally comprise aplurality of insecticides. Insecticides include oils, emulsifers,detergents, soaps, microorganisms like fungi, bacteria, bacteriophages,and viruses, abrasives, toxins, and poisons. Non-limiting examples of aninsecticide include a organochlorine, such as, e.g., Aldrin, Chlordane,Chlordecone, DDT, Dieldrin, Endosulfan, Endrin, Heptachlor,Hexachlorobenzene, Lindane (gamma-hexachlorocyclohexane), Methoxychlor,Mirex, Pentachlorophenol, and TDE; an organophosphate, such as, e.g.,Acephate, Azinphos-methyl, Bensulide, Chlorethoxyfos, Chlorpyrifos,Chlorpyriphos-methyl, Diazinon, Dichlorvos (DDVP), Dicrotophos,Dimethoate, Disulfoton, Ethoprop, Fenamiphos, Fenitrothion, Fenthion,Fosthiazate, Malathion, Methamidophos, Methidathion, Mevinphos,Monocrotophos, Naled, Omethoate, Oxydemeton-methyl, Parathion,Parathion-methyl, Phorate, Phosalone, Phosmet, Phostebupirim, Phoxim,Pirimiphos-methyl, Profenofos, Terbufos, Tetrachlorvinphos, Tribufos,and Trichlorfon; a carbamate, such as, e.g., Aldicarb, Bendiocarb,Carbofuran, Carbaryl, Dioxacarb, Fenobucarb, Fenoxycarb, Isoprocarb,Methomyl, and 2-(1-Methylpropyl)phenyl methylcarbamate; a pyrethroid,such as, e.g., Allethrin, Bifenthrin, Cyhalothrin, A-Cyhalothrin,Cypermethrin, Cyfluthrin, Deltamethrin, Etofenprox, Fenvalerate,Permethrin, Phenothrin, Prallethrin, Resmethrin, Tetramethrin,Tralomethrin, and Transfluthrin; a neonicotinoid, such as, e.g.,Acetamiprid, Clothianidin, Imidacloprid, Nitenpyram, Nithiazine,Thiacloprid, and Thiamethoxam; and a spinosad, such as, e.g., spinosyn Aand spinosyn B.

The present specification provides, in part, a composition comprising arepellent compound or a composition providing an additional beneficialor otherwise useful effect that is coated, encapsulated or otherwisecovered with a honeybee repellent or a composition comprising a honeybeerepellent disclosed herein. Additionally, the present specificationprovides, in part, a composition comprising a honeybee repellent or acomposition comprising a honeybee repellent disclosed herein that iscoated, encapsulated or otherwise covered with another compound orcomposition providing an additional beneficial or otherwise usefuleffect. The compositions disclosed herein are formulated to repelhoneybees from a location where the compositions were intentionally orunintentionally deposited and at the same time provide an additionalbeneficial or otherwise useful effect.

When used to coat another substance, a honeybee repellent or compositioncomprising a honeybee repellent disclosed herein, or a compound orcomposition providing an additional beneficial or otherwise usefuleffect disclosed herein are formulated in a manner that will allow therepellent, compound, or compositions thereof to adhere to the othersubstance. Typically, a repellent, a compound, or a composition thereofare mixed with a coating material and processed into a formulation suchas, e.g., a solid, a gel, a liquid, a suspension in aqueous ornon-aqueous medium, an emulsion, or a foam. Such coating materials andadhering methods are known to a person of ordinary skill in the art.

For example, a honeybee repellent can be mixed with a wax and theresulting mixture is then adhered to a compound providing an additionalbeneficial or otherwise useful effect in a manner that ensures thecompound is coated, encapsulated or otherwise covered by the mixture. Inone aspect, a honeybee repellent can be mixed with a wax and theresulting mixture is then adhered to a seed in a manner that ensures theseed is coated, encapsulated or otherwise covered by the mixture. Inanother aspect, a honeybee repellent can be mixed with a wax and theresulting mixture is then adhered to an insecticide in a manner thatensures the insecticide is coated, encapsulated or otherwise covered bythe mixture. In yet another aspect, a honeybee repellent and aninsecticide can be mixed with a wax and the resulting mixture is thenadhered to a seed in a manner that ensures the seed is coated,encapsulated or otherwise covered by the mixture.

In another embodiment, an appropriate amount of a honeybee repellentdisclosed herein can be dissolved into an appropriate compatible solventand the resulting mixture is then adhered to a compound providing anadditional beneficial or otherwise useful effect in a manner thatensures the compound is coated, encapsulated or otherwise covered by themixture. The solvent employed is typically a volatile solvent (i.e.,having a boiling point of about 100° C. or less) that will evaporateover a period of time. In one aspect, a honeybee repellent can be mixedwith a solvent and the resulting mixture is then adhered to a seed in amanner that ensures the seed is coated, encapsulated or otherwisecovered by the mixture. In another aspect, a honeybee repellent can bemixed with a solvent and the resulting mixture is then adhered to aninsecticide in a manner that ensures the insecticide is coated,encapsulated or otherwise covered by the mixture. In yet another aspect,a honeybee repellent and an insecticide can be mixed with a solvent andthe resulting mixture is then adhered to a seed in a manner that ensuresthe seed is coated, encapsulated or otherwise covered by the mixture.

In one aspect of this embodiment, one or more insecticides, pesticides,fungicides, fertilizers of a micronutrient or macronutrient nature,herbicides, feeding inhibitors, insect molting, insect mating, insectmaturation inhibitors, nematocides, nutritional or horticulturalsupplements, larvicides, seeds, and any combination thereof is coated,encapsulated or otherwise covered with one or more honeybee repellentsor compositions comprising a honeybee repellent disclosed herein.

In another aspect of this embodiment, a honeybee repellent orcompositions disclosed herein is coated, encapsulated or otherwisecovered with one or more insecticides, pesticides, fungicides,fertilizers of a micronutrient or macronutrient nature, herbicides,feeding inhibitors, insect molting, insect mating, insect maturationinhibitors, nematocides, nutritional or horticultural supplements,larvicides, seeds, and any combination thereof.

In yet another aspect of this embodiment, seeds are coated, encapsulatedor otherwise covered with one or more honeybee repellents orcompositions comprising a honeybee repellent disclosed herein. Thesecompositions are formulated to repel honeybees from the seed, and thusfrom a field, yard, pot, area, or body of water onto which the seedswere intentionally or unintentionally present.

In still another aspect of this embodiment, seeds are coated,encapsulated or otherwise covered with one or more honeybee repellentsor compositions comprising a honeybee repellent disclosed herein and oneor more insecticides, pesticides, fungicides, fertilizers of amicronutrient or macronutrient nature, herbicides, feeding inhibitors,insect molting, insect mating, insect maturation inhibitors,nematocides, nutritional or horticultural supplements, or larvicides.These compositions are formulated to repel honeybees from the seed, andthus from a field, yard, pot, area, or body of water onto which theseeds were be intentionally or unintentionally present as well asprovide an additional beneficial or otherwise useful effect.

In another embodiment, a honeybee repellent or composition disclosedherein is incorporated into a device. As used herein, the term “device”refers to any device designed to house and/or shelter, a honeybeerepellent or compositions disclosed herein. A device disclosed hereinmay be a container, holder or other solid support onto or into which ahoneybee repellent or composition disclosed herein. A device disclosedherein may be made form any biological or synthetic material, including,without limitation, paper, filter paper, wood, cork, cotton, plastic,polymer, metal, or glass.

Aspects of the present specification disclose a use of a honeybeerepellent disclosed herein to repel a honeybee from a location treatedwith the honeybee repellent. In one embodiment, the disclosed use is ause of a honeybee repellent disclosed herein to repel a honeybee fromforaging and/or collecting nectar from a flower of a plant treated withthe honeybee repellent. In another embodiment, the disclosed use is ause of a honeybee repellent disclosed herein to repel a honeybee from astructure treated with the honeybee repellent.

Aspects of the present specification disclose a method of treating alocation by applying a honeybee repellent disclosed herein, wherein suchapplication repels a honeybee from the treated location. In oneembodiment, the disclosed method is a method of treating a plant byapplying a honeybee repellent disclosed herein, wherein such applicationrepels a honeybee from foraging and/or collecting nectar from a flowerof the treated plant. In another embodiment, the disclosed method is amethod of treating a structure by applying a honeybee repellentdisclosed herein, wherein such application repels a honeybee from thetreated structure.

Aspects of the present specification disclose a method of reducing orpreventing a honeybee foraging to a location by applying a honeybeerepellent or composition disclosed herein, wherein such applicationrepels honeybees from the location, thereby reducing or preventing thehoneybee foraging. In one embodiment, the disclosed method is a methodof treating a plant by applying a honeybee repellent or compositiondisclosed herein, wherein such application repels a honeybee fromforaging for a meal in the vicinity of the treated plant, flower, orseed. In another embodiment, the disclosed method is a method oftreating a structure by applying a honeybee repellent or compositiondisclosed herein, wherein such application repels a honeybee fromforaging for a meal in the vicinity of the treated structure.

As used herein, the term “location” refers to any site to which movementof a honeybee is to be retarded. A location includes, by way of example,a plant or group of plants or part of a plant, a particular area ofland, or a man-made structure, such as, e.g., a commercial building, ahouse, a shed, or other physical structure. As used herein, the term“plant” refers to any living organism belonging to the Kingdom Plantae.Non-limiting examples include trees, flowering plant, herbs, bushes,grasses, vines, ferns, mosses, and green algae. As used herein, the term“flower” is synonymous with “bloom” or “blossom” and refers thereproductive structure found in angiosperms. As used herein, the term“crop plant” refers to a plant that produces a crop. Non-limitingexamples include are plants that produce fruits, seeds, nuts, grains,oil, wood, and fibers. As used herein, the term “crop” refers to a plantproduct which is of economical value. Non-limiting examples include arefruits, seeds, nuts, grains, oil, wood, and fibers.

A honeybee repellent or composition disclosed herein is applied to alocation by any method that can dispense to a location an amount ofhoneybee repellent effective in repelling a honeybee. A method ofapplication is not critical and many well known methods can be used. Inone embodiment, an appropriate amount of a honeybee repellent orcomposition disclosed herein can be dissolved into an appropriatecompatible solvent and dispensed as a solution onto the intendedlocation. The solvent employed is typically a volatile solvent (i.e.,having a boiling point of about 100° C. or less) that will evaporateover a period of time. In another embodiment, an appropriate amount of ahoneybee repellent or composition disclosed herein can be combined withan appropriate propellant and used as a spray for application onto theintended location.

In another embodiment, a honeybee repellent or composition disclosedherein can be impregnated into a compatible matrix. As used herein, theterm “compatible matrix” refers to any material in which one or morerepellent compounds disclosed herein are either soluble or miscible andwhere the material does not significantly alter or degrade theattractant activity of the one or more repellent compound. In aspects ofthis embodiment, a compatible matrix does not significantly alter ordegrade an attractant activity of one or more honeybee repellents over aperiod of, e.g., at least 7 days, at least 14 days, at least 21 days, atleast 28 days, at least 35 days, at least 42 days, at least 49 days, atleast 56 days, or at least 63 days. Impregnation of a repellent compoundinto the compatible matrix can be achieved by any well known methodsknown in the art. For example, a honeybee repellent can be dissolvedinto a compatible volatile solvent and the resulting solution added tothe matrix whereupon evaporation of the solvent results in impregnationof the repellent compound into the compatible matrix. In this regard,the matrix can be cotton twine, polymers such as, e.g., polyvinyls,polyisoprenes, polyethylene, polypropylene or copolymers thereof, orpolybutenes. In another example, a compatible matrix is thinned byheating and then a repellent compound is added directly thereto. Themixture can then be combined with twine or other compatible matrices. Acompatible matrix disclosed herein may be employed by itself orincorporated into a device used to house the matrix.

In another embodiment, a honeybee repellent or composition disclosedherein can be incorporated into a controlled-release device whichdispenses a honeybee repellent and/or other beneficial compound overtime in a regulated or predictable manner. A controlled-release devicedisclosed herein may be employed by itself or incorporated into anotherdevice used to house the controlled-release device.

One type of controlled-release device is a “reservoir” device where ahoneybee repellent or composition forms a core surrounded by an inertdiffusion barrier. An inert diffusion barrier includes membranes whichare non-porous, homogeneous polymeric films, through which transportoccurs by a process of dissolution of the permeating species in thepolymer at one interface and diffusion down a gradient in thermodynamicactivity. These membranes are usually referred to as solution-diffusionmembranes. Another class inert diffusion barrier includes the porousand/or fibrous barriers such as, for example, hollow fibers, porousand/or fibrous materials, in which a repellent compound diffuses mainlyby capillary forces. Other less common reservoir devices are designed toenable diffusion to take place by mechanical pumping or under externalforces, such as, e.g., gravity, electrical field, vacuum, or centrifugalforces. A reservoir device can exist in a variety of shapes, and can bedegradable or non-degradable.

In an aspect of this embodiment, a reservoir device is a microcapsulecomprising a core of a honeybee repellent or composition disclosedherein surrounded by a coating or shell of, e.g., a polyvinyl chloride(PVC)-polyvinyl acetate (PVA) plastic. Size typically varies from about1 μm to about 1000 μm and can have irregular or geometric shapes. Corepayload usually varies from 0.1 to 98 weight percent. Encapsulationprocesses are often loosely classified as either chemical or mechanical.Examples of chemical processes include but are not limited to complexcoacervation, polymer-polymer incompatibility, interfacialpolymerization in liquid media, in situ polymerization, in-liquiddrying, thermal and ionic gelation in liquid media, desolvation inliquid media, starch-based chemistry processes, trapping incyclodextrins, and formation of liposomes. Examples of mechanicalprocesses include but are not limited to spray drying, spray chilling,fluidized bed, electrostatic deposition, centrifugal extrusion, spinningdisk or rotational suspension separation, annular-jet encapsulation,polymerization at liquid-gas or solid-gas interface, solventevaporation, pressure extrusion or spraying into solvent extractionbath.

Another type of controlled-release device is a “monolithic” device wherea honeybee repellent or composition is dissolved or dispersed throughouta substantially inert matrix from which the repellent compound and/orother beneficial compound is gradually released. Non-limiting examplesof matrices included in a monolithic device include various gels, waxes,gelatins, natural resins, rubbers, elastomers, synthetic and naturalpolymers. A monolithic device can exist in a variety of shapes, and canbe degradable or non-degradable. Size can vary depending on theapplication. For example, a monolithic device can be produced as amicrocapsule having a size of about 1 μm to about 1000 μm with irregularor geometric shapes. As another example, a monolithic device can have asize of about 1 mm to about 10 cm with irregular or geometric shape.

A controlled-release device disclosed herein can be a liquid compositionor a solid composition. A liquid sustained-release formulation includesa honeybee repellent or composition disclosed herein, a solvent, andtypically further comprise surface active agents to render thecomposition readily dispersible in water, such agents include a wettingagent, an emulsifying agent, or a dispersing agent. In one embodiment, aliquid form of a sustained-release formulation is an emulsionformulation, such as, e.g., a water in oil (w/o) emulsion or oil inwater (o/w) emulsion. Non-limiting examples of oils include vegetableoils and mineral oils. Droplet size can vary from the nanometer scale(colloidal dispersion) to several hundred microns. A variety ofsurfactants and thickeners are usually incorporated in the formulationto modify the size of the droplets, stabilize the emulsion, and modifythe release.

A solid form of controlled-release device comprises a solid substratelike porous particulates such as silica, perlite, talc, clay,pyrophyllite, diatomaceous earth, gelatin and gels, polymers (e.g.,polyurea, polyurethane, polyamide, polyester, etc.), polymericparticles, or cellulose. These include, for example, hollow fibers,hollow tubes or tubing which release a repellent compound disclosedherein through the walls, capillary tubing which releases the compoundout of an opening in the tubing, polymeric blocks of different shapes,e.g., strips, blocks, tablets, discs, which release the compound out ofthe polymer matrix, membrane systems which hold the repellent compoundwithin an impermeable container and release it through a measuredpermeable membrane, and combinations of the foregoing. Examples of otherdispensing means are polymer laminates, polyvinyl chloride pellets, andmicrocapillaries.

Controlled release can also be achieved by a number of other methodssuch as, e.g., complexation of a honeybee repellent or composition,slowly dissolving coatings, erosion, microbial action, or use ofderivatives or new compounds of reduced solubility or volatility.

In aspects of this embodiment, a controlled-release device releases ahoneybee repellent or composition disclosed herein with substantiallyzero order release kinetics over a period of, e.g., about 7 days, about15 days, about 30 days, about 45 days, about 60 days, about 75 days, orabout 90 days. In other aspects of this embodiment, a controlled-releasedevice releases a honeybee repellent or composition disclosed hereinwith substantially zero order release kinetics over a period of, e.g.,at least 7 days, at least 15 days, at least 30 days, at least 45 days,at least 60 days, at least 75 days, or at least 90 days. In otheraspects of this embodiment, a controlled-release device releases ahoneybee repellent or composition disclosed herein with substantiallyzero order release kinetics over a period of between, e.g., about 7 daysto about 30 days, about 15 days to about 45 days, about 30 days to about60 days, about 45 days to about 75 days, or about 60 days to about 90days.

In aspects of this embodiment, a controlled-release device releases ahoneybee repellent or composition disclosed herein with substantiallyfirst order release kinetics over a period of, e.g., about 7 days, about15 days, about 30 days, about 45 days, about 60 days, about 75 days, orabout 90 days. In other aspects of this embodiment, a controlled-releasedevice releases a honeybee repellent or composition disclosed hereinwith substantially first order release kinetics over a period of, e.g.,at least 7 days, at least 15 days, at least 30 days, at least 45 days,at least 60 days, at least 75 days, or at least 90 days. In otheraspects of this embodiment, a controlled-release device releases ahoneybee repellent or composition disclosed herein with substantiallyfirst order release kinetics over a period of between, e.g., about 7days to about 30 days, about 15 days to about 45 days, about 30 days toabout 60 days, about 45 days to about 75 days, or about 60 days to about90 days.

Regardless of the method of application, the amount of a honeybeerepellent disclosed herein used is a repellent effective amount, i.e.,it is an amount sufficient to retard the movement of honeybees to theselected location. In aspects of this embodiment, a honeybee repellentdisclosed herein is applied at a rate of, e.g., about 0.01 mg/m², about0.025 mg/m², about 0.05 mg/m², about 0.075 mg/m², about 0.1 mg/m², about0.25 mg/m², about 0.5 mg/m², about 0.75 mg/m², about 1 mg/m², about 2.5mg/m², about 5 mg/m², about 7.5 mg/m², or about 10 mg/m². In otheraspects of this embodiment, a honeybee repellent disclosed herein isapplied at a rate of, e.g., at least 0.01 mg/m², at least 0.025 mg/m²,at least 0.05 mg/m², at least 0.075 mg/m², at least 0.1 mg/m², at least0.25 mg/m², at least 0.5 mg/m², at least 0.75 mg/m², at least 1 mg/m²,at least 2.5 mg/m², at least 5 mg/m², at least 7.5 mg/m², or at least 10mg/m². In yet other aspects of this embodiment, a honeybee repellentdisclosed herein is applied at a rate of, between e.g., about 0.01 mg/m²to about 10 mg/m², about 0.01 mg/m² to about 1 mg/m², about 0.01 mg/m²to about 0.1 mg/m², about 0.05 mg/m² to about 10 mg/m², about 0.05 mg/m²to about 1 mg/m², about 0.05 mg/m² to about 0.1 mg/m², about 0.05 mg/m²to about 5 mg/m², or about 0.05 mg/m² to about 0.5 mg/m².

Aspects of the present specification may also be described as follows:

-   1. A honeybee repellent that substantially mimics a repellent    chemosensory cue of 2-heptanone, wherein the compound is not    2-heptanone.-   2. The honeybee repellent according to embodiment 1, wherein the    honeybee repellent has a repellent chemosensory cue that is at least    75%, at least 80%, at least 85%, at least 90%, at least 95%, or at    least 97% that of the repellent chemosensory cue of 2-heptanone.-   3. The honeybee repellent according to embodiment 1, wherein the    honeybee repellent has a repellent chemosensory cue that is at least    one-fold, at least two-fold, at least three-fold, at least four    fold, at least five-fold, at least six-fold, at least seven-fold, at    least eight-fold, at least nine-fold, at least 10-fold, at least    20-fold, at least 30-fold, at least 40-fold, at least 50-fold, at    least 60-fold, at least 70-fold, at least 80-fold, at least 90-fold,    at least 100-fold, at least 125-fold, at least 150-fold, at least    175-fold, or at least 200-fold that of the repellent chemosensory    cue of 2-heptanone.-   4. A honeybee repellent having a honeybee repellency activity,    wherein the compound is not 2-heptanone.-   5. The honeybee repellent according to embodiment 4, wherein the    honeybee repellent repels honeybees by at least 10%, at least 15%,    at least 20%, at least 25%, at least 30%, at least 35%, at least    40%, at least 45%, at least 50%, at least 55%, at least 60%, at    least 65%, at least 70%, at least 75%, at least 80%, at least 85%,    at least 90%, or at least 95%, as compared to not having the    honeybee repellent present.-   6. The honeybee repellent according to embodiment 4 or 5, wherein    the honeybee repellent reduces a honeybee interaction with a mammal,    a plant, structure, and/or location.-   7. The honeybee repellent according to any one of embodiments 4-6,    wherein the honeybee repellent reduces a honeybee interaction with a    mammal, a plant, structure, and/or location by at least 10%, at    least 15%, at least 20%, at least 25%, at least 30%, at least 35%,    at least 40%, at least 45%, at least 50%, at least 55%, at least    60%, at least 65%, at least 70%, at least 75%, at least 80%, at    least 85%, at least 90%, or at least 95%.-   8. The honeybee repellent according to any one of embodiments 4-7,    wherein the honeybee repellent reduces an ability of a honeybee to    obtain a meal and/or nectar from a plant.-   9. The honeybee repellent according to any one of embodiments 4-8,    wherein the honeybee repellent reduces an ability of a honeybee to    obtain a meal and/or nectar from a plant by at least 10%, at least    15%, at least 20%, at least 25%, at least 30%, at least 35%, at    least 40%, at least 45%, at least 50%, at least 55%, at least 60%,    at least 65%, at least 70%, at least 75%, at least 80%, at least    85%, at least 90%, or at least 95%.-   10. The honeybee repellent according to any one of embodiments 1-9,    wherein the honeybee repellent is more stable than 2-heptanone.-   11. The honeybee repellent according to any one of embodiments 1-10,    wherein the honeybee repellent is less volatile than 2-heptanone.-   12. The honeybee repellent according to any one of embodiments 1-11,    wherein the honeybee repellent has a half-life of at least one day,    at least three days, at least five days, at least one week, at least    two weeks, at least three weeks, at least one month, at least two    months, or at least three months.-   13. The honeybee repellent according to embodiments 1-11, wherein    the honeybee repellent has a half-life about one day to about seven    days, about three days to about seven days, about five days to about    seven days, about one week to about four weeks, about two weeks to    about four weeks, about three weeks to about four weeks, about one    month to about four months, about two months to about four months,    or about three months to about four months.-   14. The honeybee repellent according to any one of embodiments 1-13,    wherein the honeybee repellent has a binding affinity for a honeybee    OBP that is substantially the same as the binding affinity of    2-heptanone, wherein the compound is not 2-heptanone.-   15. The honeybee repellent according to any one of embodiments 1-14,    wherein the honeybee repellent has a binding affinity for a honeybee    OBP that is at least 75%, at least 80%, at least 85%, at least 90%,    at least 95%, or at least 97% that of the binding affinity of    2-heptanone for that honeybee OBP.-   16. The honeybee repellent according to any one of embodiments 1-15,    wherein the honeybee repellent has a dissociation equilibrium    constant that is greater than the dissociation equilibrium constant    of 2-heptanone for that honeybee OBP by at least one-fold, at least    two-fold, at least three-fold, at least four fold, at least    five-fold, at least six-fold, at least seven-fold, at least    eight-fold, at least nine-fold, at least 10-fold, at least 20-fold,    at least 30-fold, at least 40-fold, at least 50-fold, at least    60-fold, at least 70-fold, at least 80-fold, at least 90-fold, at    least 100-fold, at least 125-fold, at least 150-fold, at least    175-fold, or at least 200-fold.-   17. The honeybee repellent according to any one of embodiments 1-16,    wherein the honeybee repellent has an association rate constant of    less than 1×10⁵ M⁻¹ s⁻¹, less than 1×10⁶ M⁻¹ s⁻¹, less than 1×10⁷M⁻¹    s⁻¹, or less than 1×10⁸ M⁻¹ s⁻¹.-   18. The honeybee repellent according to any one of embodiments 1-16,    wherein the honeybee repellent has an association rate constant of    more than 1×10⁵ M⁻¹ s⁻¹, more than 1×10⁶ M⁻¹ s⁻¹, more than 1×10⁷    M⁻¹ s⁻¹, or more than 1×10⁸ M⁻¹ s⁻¹.-   19. The honeybee repellent according to any one of embodiments 1-18,    wherein the honeybee repellent has a disassociation rate constant of    less than 1×10⁻³ s⁻¹, less than 1×10⁻⁴ s⁻¹, or less than 1×10⁻⁵ s⁻¹.-   20. The honeybee repellent according to any one of embodiments 1-18,    wherein the honeybee repellent has a disassociation rate constant of    more than 1×10⁻³ s⁻¹, more than 1×10⁻⁴ s⁻¹, or more than 1×10⁻⁵ s⁻¹.-   21. The honeybee repellent according to any one of embodiments 1-20,    wherein the honeybee repellent has an equilibrium disassociation    constant of less than 0.500 nM, less than 0.450 nM, less than 0.400    nM, less than 0.350 nM, less than 0.300 nM, less than 0.250 nM, less    than 0.200 nM, less than 0.150 nM, less than 0.100 nM, or less than    0.050 nM.-   22. The honeybee repellent according to any one of embodiments 1-20,    wherein the honeybee repellent has an equilibrium disassociation    constant of more than 0.500 nM, more than 0.450 nM, more than 0.400    nM, more than 0.350 nM, more than 0.300 nM, more than 0.250 nM, more    than 0.200 nM, more than 0.150 nM, more than 0.100 nM, or more than    0.050 nM.-   23. The honeybee repellent according to any one of embodiments 1-22,    wherein the honeybee repellent has a structure of formula I    disclosed herein-   24. The honeybee repellent according to any one of embodiments 1-23,    wherein the honeybee repellent wherein the compound has a structure    of formula Ia disclosed herein.-   25. The honeybee repellent according to any one of embodiments 1-24,    wherein the honeybee repellent is    1-benzyl-4-(4-methoxy-2,3-dimethylbenzyl) piperazine,    1-[(6-nitro-1,3-benzodioxol-5-yl)methyl]-4-phenylpiperazine,    4-[4-nitro-3-(2-phenoxyethoxy)phenyl]morpholine,    1-(3-chlorophenyl)-4-[(6-nitro-1,3-benzodioxol-5-yl)methyl]piperazine,    1-(4-methoxybenzyl)-4-(3-methylbenzyl)piperazine,    4-(4-methoxy-2,3-dimethylbenzyl) morpholine,    1-benzyl-4-(4-methoxy-3-methylbenzyl)piperazine,    1-(4-methoxy-2,3-dimethylbenzyl)-4-methyl piperazine,    1-(4-methoxy-2,3-dimethylbenzyl)-4-methylpiperazine,    1-(1,3-benzodioxol-5-ylmethyl)-4-(4,5-dimethoxy-2-nitrobenzyl)piperazine,    1-(2,3-dimethylphenyl)-4-(4-methoxy-2,3-dimethylbenzyl)piperazine,    1-(4-methoxy-2,3-dimethylbenzyl)-4-phenylpiperazine,    1-[3-(4-iodophenoxy)propyl]piperidine,    1-(4-methoxy-2,3-dimethylbenzyl)-4-(4-methylphenyl)piperazine, or    any combination thereof.-   26. The honeybee repellent according to any one of embodiments 1-22,    wherein the honeybee repellent has a structure of formula II    disclosed herein.-   27. The honeybee repellent according to any one of embodiments 1-22    or 26, wherein the honeybee repellent has a structure of formula IIa    disclosed herein.-   28. The honeybee repellent according to any one of embodiments 1-22,    26 or 27, wherein the honeybee repellent has is    2-{[(2-methoxy-1-naphthyl)methylene]amino}-1H-isoindole-1,3(2H)-dione,    2-[(2-ethoxybenzylidene)amino]-1H-isoindole-1,3(2H)-dione, or any    combination thereof.-   29. The honeybee repellent according to any one of embodiments 1-22    or 26, wherein the honeybee repellent has a structure of formula IIb    disclosed herein.-   30. The honeybee repellent according to any one of embodiments 1-22,    26 or 29, wherein the honeybee repellent is    3-ethyl-5-(4-hydroxybenzylidene)-2-thioxo-1,3-thiazolidin-4-one,    3-butyl-5-(3-hydroxybenzylidene)-2-thioxo-1,3-thiazolidin-4-one,    5-(3-bromo-4-methoxybenzylidene)-3-methyl-2-thioxo-1,3-thiazolidin-4-one,    5-(5-bromo-2-hydroxybenzylidene)-3-ethyl-2-thioxo-1,3-thiazolidin-4-one,    or any combination thereof.-   31. The honeybee repellent according to any one of embodiments 1-22    or 26, wherein the honeybee repellent has a structure of formula IIc    disclosed herein.-   32. The honeybee repellent according to any one of embodiments 1-22,    26 or 31, wherein the honeybee repellent is    2-phenyl-4-(2-thienylmethylene)-1,3-oxazol-5(4H)-one.-   33. The honeybee repellent according to any one of embodiments 1-22    or 26, wherein the honeybee repellent has a structure of formula IId    disclosed herein.-   34. The honeybee repellent according to any one of embodiments 1-22,    26 or 33, wherein the honeybee repellent is    5-(4-chlorobenzylidene)-3-(2-methoxyphenyl)-2-thioxo-1,3-thiazolidin-4-one,    3-(4-bromophenyl)-5-(4-hydroxybenzylidene)-2-thioxo-1,3-thiazolidin-4-one,    4-[3-bromo-4-(dimethylamino)benzylidene]-2-(2-methoxyphenyl)-1,3-oxazol-5(4H)-one,    or any combination thereof.-   35. The honeybee repellent according to any one of embodiments 1-22,    wherein the honeybee repellent has a structure of formula III    disclosed herein.-   36. The honeybee repellent according to any one of embodiments 1-22    or 35, wherein the honeybee repellent is    4-[2-(4-nitrophenyl)vinyl]phenol,    3-{2-[(4-fluorobenzyl)amino]phenyl}-2(1H)-quinoxalinone,    4-bromo-3-chlorophenyl)(4-ethoxybenzylidene)amine,    4-[(2-chloro-5-nitrobenzylidene)amino]phenol,    2-[(2-hydroxy-3,5-diiodobenzylidene)amino]-4,6-dimethylphenol,    (2-methoxybenzyl)(4-methoxy-3-biphenylyl)amine,    2-{[(5-ethyl-2-hydroxyphenyl)imino]methyl}-4,6-diiodophenol, or any    combination thereof.-   37. The honeybee repellent according to any one of embodiments 1-22,    wherein the honeybee repellent has a structure of formula IV    disclosed herein.-   38. The honeybee repellent according to any one of embodiments 1-22    or 37, wherein the honeybee repellent is    3-methoxy-4-(4-nitrophenoxy)benzaldehyde oxime.-   39. The honeybee repellent according to any one of embodiments 1-22,    wherein the honeybee repellent has a structure of formula V    disclosed herein.-   40. The honeybee repellent according to any one of embodiments 1-22    or 39, wherein the honeybee repellent has a structure of formula Va    disclosed herein.-   41. The honeybee repellent according to any one of embodiments 1-22    39 or 40, wherein the honeybee repellent is    1-butyl-4-hydroxy-2-oxo-N-(2-pyridinylmethyl)-1,2-dihydro-3-quinolinecarboxamide,    2-acetyl-4-chlorophenyl 4-methylbenzoate,    N-(2-fluorobenzyl)-4-hydroxy-2-oxo-1-propyl-1,2-dihydro-3-quinolinecarboxamide,    ethyl 2-(benzoylamino)-5-ethyl-3-thiophenecarboxylate, or any    combination thereof.-   41. The honeybee repellent according to any one of embodiments 1-22,    wherein the honeybee repellent has a structure of formula VI    disclosed herein.-   42. The honeybee repellent according to any one of embodiments 1-22    or 41, wherein the honeybee repellent is    2-(benzoylamino)-N-(2-chlorophenyl)benzamide.-   43. The honeybee repellent according to any one of embodiments 1-22,    wherein the honeybee repellent has a structure of formula VII    disclosed herein.-   44. The honeybee repellent according to any one of embodiments 1-22    or 43, wherein the honeybee repellent is ethyl    2-(3-aminophenyl)-4-quinolinecarboxylate.-   45. The honeybee repellent according to any one of embodiments 1-22,    wherein the honeybee repellent has a structure of formula VIII    disclosed herein.-   46. The honeybee repellent according to any one of embodiments 1-22    or 45, wherein the honeybee repellent is    1-(4-bromobenzoyl)-2,2,4-trimethyl-1,2-dihydroquinoline.-   47. The honeybee repellent according to any one of embodiments 1-22,    wherein the honeybee repellent has a structure of formula IX    disclosed herein.-   48. The honeybee repellent according to any one of embodiments 1-22    or 47, wherein the honeybee repellent is dimethyl    2-(1,2,2-trimethyl-3-thioxo-2,3-dihydro-4(1H)-quinolinylidene)-1,3-dithiole-4,5-dicarboxylate,    dimethyl    2-(2,2,7-trimethyl-3-thioxo-2,3-dihydro-4(1H)-quinolinylidene)-1,3-dithiole-4,5-dicarboxylate,    or any combination thereof.-   49. The honeybee repellent according to any one of embodiments 1-22,    wherein the honeybee repellent has a structure of formula X    disclosed herein.-   50. The honeybee repellent according to any one of embodiments 1-22    or 49, wherein the honeybee repellent is    N-(4-methoxy-2,3-dimethylbenzyl)-N,N′,N′-trimethyl-1,2-ethanediamine.-   51. The honeybee repellent according to any one of embodiments 1-22,    wherein the honeybee repellent has a structure of formula XI    disclosed herein.-   52. The honeybee repellent according to any one of embodiments 1-22    or 51, wherein the honeybee repellent is    1,2,3-trichloro-4-(isopropylamino)anthra-9,10-quinone.-   53. The honeybee repellent according to any one of embodiments 1-22,    wherein the honeybee repellent has a structure of formula XII    disclosed herein.-   54. The honeybee repellent according to any one of embodiments 1-22    or 53, wherein the honeybee repellent is    [1-(3-nitrobenzyl)-3-piperidinyl]methyl 3-phenylacrylate.-   55. The honeybee repellent according to any one of embodiments 1-22,    wherein the honeybee repellent has a structure of formula XIII    disclosed herein.-   56. The honeybee repellent according to any one of embodiments 1-22    or 55, wherein the honeybee repellent has a structure of formula    XIIIa disclosed herein.-   57. The compound according to any one of embodiments 1-22, 55 or 56,    wherein the compound is    (3-amino-4,6-dimethylthieno[2,3-b]pyridin-2-yl)    (4-chlorophenyl)methanone,    (4-bromophenyl)(5-methoxy-2-methyl-1-benzofuran-3-yl)methanone,    1-(4-methoxyphenyl)-3-(2-methyl-1H-indol-3-yl)-2-propen-1-one,    2-[2-(3,5-dimethyl-1H-pyrazol-1-yl)-6-phenyl-4-pyrimidinyl]phenol,    or any combination thereof.-   58. The honeybee repellent according to any one of embodiments 1-22    or 55, wherein the honeybee repellent has a structure of formula    XIIIb disclosed herein.-   59. The compound according to any one of embodiments 1-22, 55 or 58,    wherein the honeybee repellent is    2-[2-(3,5-dimethyl-1H-pyrazol-1-yl)-6-phenyl-4-pyrimidinyl]phenol.-   60. The honeybee repellent according to any one of embodiments 1-22,    wherein the honeybee repellent has a structure of formula XV    disclosed herein.-   61. The honeybee repellent according to any one of embodiments 1-22    or 60, wherein the honeybee repellent has a structure of formula XVa    disclosed herein.-   62. The honeybee repellent according to any one of embodiments 1-22    or 60, wherein the honeybee repellent has a structure of formula XVb    disclosed herein.-   63. The honeybee repellent according to any one of embodiments 1-22    or 60, wherein the honeybee repellent has a structure of formula XVc    disclosed herein.-   64. The honeybee repellent according to any one of embodiments 1-22    or 60, wherein the honeybee repellent has a structure of formula XVd    disclosed herein.-   65. The honeybee repellent according to any one of embodiments 1-22,    wherein the honeybee repellent is an optionally substituted    1-benzyl-4-(4-methoxy-2,3-dimethylbenzyl) piperazine, optionally    substituted    1-[(6-nitro-1,3-benzodioxol-5-yl)methyl]-4-phenylpiperazine, an    optionally substituted    4-[4-nitro-3-(2-phenoxyethoxy)phenyl]morpholine, an optionally    substituted    1-(3-chlorophenyl)-4-[(6-nitro-1,3-benzodioxol-5-yl)methyl]piperazine,    an optionally substituted    1-(4-methoxybenzyl)-4-(3-methylbenzyl)piperazine, an optionally    substituted 4-(4-methoxy-2,3-dimethylbenzyl) morpholine, an    optionally substituted    1-benzyl-4-(4-methoxy-3-methylbenzyl)piperazine, an optionally    substituted 1-(4-methoxy-2,3-dimethylbenzyl)-4-methyl piperazine, an    optionally substituted    1-(4-methoxy-2,3-dimethylbenzyl)-4-methylpiperazine, an optionally    substituted    1-(1,3-benzodioxol-5-ylmethyl)-4-(4,5-dimethoxy-2-nitrobenzyl)piperazine,    an optionally substituted    1-(2,3-dimethylphenyl)-4-(4-methoxy-2,3-dimethylbenzyl)piperazine,    an optionally substituted    1-(4-methoxy-2,3-dimethylbenzyl)-4-phenylpiperazine, an optionally    substituted 1-[3-(4-iodophenoxy)propyl]piperidine, an optionally    substituted    1-(4-methoxy-2,3-dimethylbenzyl)-4-(4-methylphenyl)piperazine, an    optionally substituted    2-{[(2-methoxy-1-naphthyl)methylene]amino}-1H-isoindole-1,3(2H)-dione,    an optionally substituted    2-[(2-ethoxybenzylidene)amino]-1H-isoindole-1,3(2H)-dione, an    optionally substituted    3-ethyl-5-(4-hydroxybenzylidene)-2-thioxo-1,3-thiazolidin-4-one, an    optionally substituted    3-butyl-5-(3-hydroxybenzylidene)-2-thioxo-1,3-thiazolidin-4-one, an    optionally substituted    5-(3-bromo-4-methoxybenzylidene)-3-methyl-2-thioxo-1,3-thiazolidin-4-one,    an optionally substituted    5-(5-bromo-2-hydroxybenzylidene)-3-ethyl-2-thioxo-1,3-thiazolidin-4-one,    an optionally substituted    2-phenyl-4-(2-thienylmethylene)-1,3-oxazol-5(4H)-one, an optionally    substituted    5-(4-chlorobenzylidene)-3-(2-methoxyphenyl)-2-thioxo-1,3-thiazolidin-4-one,    an optionally substituted    3-(4-bromophenyl)-5-(4-hydroxybenzylidene)-2-thioxo-1,3-thiazolidin-4-one,    an optionally substituted    4-[3-bromo-4-(dimethylamino)benzylidene]-2-(2-methoxyphenyl)-1,3-oxazol-5(4H)-one,    an optionally substituted 4-[2-(4-nitrophenyl)vinyl]phenol, an    optionally substituted    3-{2-[(4-fluorobenzyl)amino]phenyl}-2(1H)-quinoxalinone, an    optionally substituted    4-bromo-3-chlorophenyl)(4-ethoxybenzylidene)amine, an optionally    substituted 4-[(2-chloro-5-nitrobenzylidene)amino]phenol, an    optionally substituted    2-[(2-hydroxy-3,5-diiodobenzylidene)amino]-4,6-dimethylphenol, an    optionally substituted    (2-methoxybenzyl)(4-methoxy-3-biphenylyl)amine, an optionally    substituted    2-{[(5-ethyl-2-hydroxyphenyl)imino]methyl}-4,6-diiodophenol, an    optionally substituted 3-methoxy-4-(4-nitrophenoxy)benzaldehyde    oxime. In some embodiments, a honeybee repellent may be optionally    substituted    1-butyl-4-hydroxy-2-oxo-N-(2-pyridinylmethyl)-1,2-dihydro-3-quinolinecarboxamide,    an optionally substituted 2-acetyl-4-chlorophenyl 4-methylbenzoate,    an optionally substituted    N-(2-fluorobenzyl)-4-hydroxy-2-oxo-1-propyl-1,2-dihydro-3-quinolinecarboxamide,    an optionally substituted ethyl    2-(benzoylamino)-5-ethyl-3-thiophenecarboxylate, an optionally    substituted 2-(benzoylamino)-N-(2-chlorophenyl)benzamide, an    optionally substituted ethyl    2-(3-aminophenyl)-4-quinolinecarboxylate, an optionally substituted    1-(4-bromobenzoyl)-2,2,4-trimethyl-1,2-dihydroquinoline, an    optionally substituted dimethyl    2-(1,2,2-trimethyl-3-thioxo-2,3-dihydro-4(1H)-quinolinylidene)-1,3-dithiole-4,5-dicarboxylate,    an optionally substituted dimethyl    2-(2,2,7-trimethyl-3-thioxo-2,3-dihydro-4(1H)-quinolinylidene)-1,3-dithiole-4,5-dicarboxylate,    an optionally substituted    N-(4-methoxy-2,3-dimethylbenzyl)-N,N′,N′-trimethyl-1,2-ethanediamine,    an optionally substituted    1,2,3-trichloro-4-(isopropylamino)anthra-9,10-quinone, an optionally    substituted [1-(3-nitrobenzyl)-3-piperidinyl]methyl    3-phenylacrylate, an optionally substituted    (3-amino-4,6-dimethylthieno[2,3-b]pyridin-2-yl)    (4-chlorophenyl)methanone, an optionally substituted    (4-bromophenyl)(5-methoxy-2-methyl-1-benzofuran-3-yl)methanone, an    optionally substituted    1-(4-methoxyphenyl)-3-(2-methyl-1H-indol-3-yl)-2-propen-1-one, or an    optionally substituted    2-[2-(3,5-dimethyl-1H-pyrazol-1-yl)-6-phenyl-4-pyrimidinyl]phenol.-   66. The honeybee repellent according to any one of embodiments 1-65,    wherein the honeybee repellent is not    1-benzyl-4-(4-methoxy-2,3-dimethylbenzyl) piperazine,    1-[(6-nitro-1,3-benzodioxol-5-yl)methyl]-4-phenylpiperazine,    4-[4-nitro-3-(2-phenoxyethoxy)phenyl]morpholine,    1-(3-chlorophenyl)-4-[(6-nitro-1,3-benzodioxol-5-yl)methyl]piperazine,    1-(4-methoxybenzyl)-4-(3-methylbenzyl)piperazine,    4-(4-methoxy-2,3-dimethylbenzyl) morpholine,    1-benzyl-4-(4-methoxy-3-methylbenzyl)piperazine,    1-(4-methoxy-2,3-dimethylbenzyl)-4-methyl piperazine,    1-(4-methoxy-2,3-dimethylbenzyl)-4-methylpiperazine,    1-(1,3-benzodioxol-5-ylmethyl)-4-(4,5-dimethoxy-2-nitrobenzyl)piperazine,    1-(2,3-dimethylphenyl)-4-(4-methoxy-2,3-dimethylbenzyl)piperazine,    1-(4-methoxy-2,3-dimethylbenzyl)-4-phenylpiperazine,    1-[3-(4-iodophenoxy)propyl]piperidine,    1-(4-methoxy-2,3-dimethylbenzyl)-4-(4-methylphenyl)piperazine,    2-{[(2-methoxy-1-naphthyl)methylene]amino}-1H-isoindole-1,3(2H)-dione,    2-[(2-ethoxybenzylidene)amino]-1H-isoindole-1,3(2H)-dione,    3-ethyl-5-(4-hydroxybenzylidene)-2-thioxo-1,3-thiazolidin-4-one,    3-butyl-5-(3-hydroxybenzylidene)-2-thioxo-1,3-thiazolidin-4-one,    5-(3-bromo-4-methoxybenzylidene)-3-methyl-2-thioxo-1,3-thiazolidin-4-one,    5-(5-bromo-2-hydroxybenzylidene)-3-ethyl-2-thioxo-1,3-thiazolidin-4-one,    2-phenyl-4-(2-thienylmethylene)-1,3-oxazol-5(4H)-one,    5-(4-chlorobenzylidene)-3-(2-methoxyphenyl)-2-thioxo-1,3-thiazolidin-4-one,    3-(4-bromophenyl)-5-(4-hydroxybenzylidene)-2-thioxo-1,3-thiazolidin-4-one,    4-[3-bromo-4-(dimethylamino)benzylidene]-2-(2-methoxyphenyl)-1,3-oxazol-5(4H)-one,    4-[2-(4-nitrophenyl)vinyl]phenol,    3-{2-[(4-fluorobenzyl)amino]phenyl}-2(1H)-quinoxalinone,    4-bromo-3-chlorophenyl)(4-ethoxybenzylidene)amine,    4-[(2-chloro-5-nitrobenzylidene)amino]phenol,    2-[(2-hydroxy-3,5-diiodobenzylidene)amino]-4,6-dimethylphenol,    (2-methoxybenzyl)(4-methoxy-3-biphenylyl)amine,    2-{[(5-ethyl-2-hydroxyphenyl)imino]methyl}-4,6-diiodophenol,    3-methoxy-4-(4-nitrophenoxy)benzaldehyde oxime. In some embodiments,    a honeybee repellent may be optionally substituted    1-butyl-4-hydroxy-2-oxo-N-(2-pyridinylmethyl)-1,2-dihydro-3-quinolinecarboxamide,    2-acetyl-4-chlorophenyl 4-methylbenzoate,    N-(2-fluorobenzyl)-4-hydroxy-2-oxo-1-propyl-1,2-dihydro-3-quinolinecarboxamide,    ethyl 2-(benzoylamino)-5-ethyl-3-thiophenecarboxylate,    2-(benzoylamino)-N-(2-chlorophenyl)benzamide, ethyl    2-(3-aminophenyl)-4-quinolinecarboxylate,    1-(4-bromobenzoyl)-2,2,4-trimethyl-1,2-dihydroquinoline, dimethyl    2-(1,2,2-trimethyl-3-thioxo-2,3-dihydro-4(1H)-quinolinylidene)-1,3-dithiole-4,5-dicarboxylate,    dimethyl    2-(2,2,7-trimethyl-3-thioxo-2,3-dihydro-4(1H)-quinolinylidene)-1,3-dithiole-4,5-dicarboxylate,    N-(4-methoxy-2,3-dimethylbenzyl)-N,N′,N′-trimethyl-1,2-ethanediamine,    1,2,3-trichloro-4-(isopropylamino)anthra-9,10-quinone,    [1-(3-nitrobenzyl)-3-piperidinyl]methyl 3-phenylacrylate,    (3-amino-4,6-dimethylthieno[2,3-b]pyridin-2-yl)    (4-chlorophenyl)methanone,    (4-bromophenyl)(5-methoxy-2-methyl-1-benzofuran-3-yl)methanone,    1-(4-methoxyphenyl)-3-(2-methyl-1H-indol-3-yl)-2-propen-1-one, or    2-[2-(3,5-dimethyl-1H-pyrazol-1-yl)-6-phenyl-4-pyrimidinyl]phenol,    or any combination thereof.-   67. A composition comprising a compound according to any one of    embodiments 1-66.-   68. The composition according to embodiment 67, wherein the    composition comprises a two or more different compound according to    any one of embodiments 1-66, three or more different compound    according to any one of embodiments 1-66, four or more different    compound according to any one of embodiments 1-66, or five or more    different compound according to any one of embodiments 1-66.-   69. The composition according to embodiments 67 and 68, wherein the    composition further comprises a solvent, a wetting agent, an    emulsifying agent, a carrier, a diluent, or a dispersing agent.-   70. The composition according to embodiments 67-69, wherein the    composition is a liquid form or a solid form.-   71. The composition according to embodiments 67-70, wherein the    composition further comprises one or more an adhesive, a solvent, a    wetting agent, an emulsifying agent, a carrier, a diluent, a    dispersing agent an insecticide, a pesticide, a fungicide, a    fertilizer of a micronutrient or macronutrient nature, a herbicide,    a feeding inhibitor, an insect molting inhibitor, an insect mating    inhibitor, an insect maturation inhibitor, a nematocide, a    nutritional or horticultural supplement, a larvicide, a seed, or any    combination thereof.-   72. The composition according to embodiment 71, wherein the    composition further comprises an insecticide.-   73. The composition according to embodiment 72, wherein the    insecticide is an organochlorine, an organophosphate, a carbamate, a    pyrethroid, or a neonicotinoid.-   74. The composition according to embodiment 73, wherein the    neonicotinoid is Acetamiprid, Clothianidin, Imidacloprid,    Nitenpyram, Nithiazine, Thiacloprid, or Thiamethoxam.-   75. A use of a honeybee repellent according to any one of    embodiments 1-66 or a composition according to any one of    embodiments 67-74 to repel a honeybee from a location by applying    the compound or the composition to the location.-   76. A use of a honeybee repellent according to any one embodiments    1-66 or a composition according to any one of embodiments 67-74 to    repel a honeybee from foraging and/or collecting nectar from a    flower of a plant by applying the compound or the composition to the    plant or in a location in the vicinity of the plant.-   77. A use of a honeybee repellent according to any one of    embodiments 1-66 or a composition according to any one of    embodiments 67-74 to repel a honeybee from a structure by applying    the compound or the composition to the structure or in a location in    the vicinity of the structure.-   78. A method of repelling a honeybee from a location, the method    comprising the step of applying a honeybee repellent according to    any one of embodiments 1-66 or a composition according to any one of    embodiments 67-74 to a location, wherein application of the compound    or the composition to the location repels a honeybee from the    location.-   79. A method of repelling a honeybee from a plant, the method    comprising the step of applying a honeybee repellent according to    any one of embodiments 1-66 or a composition according to any one of    embodiments 67-74 to a plant or in a location in the vicinity of the    plant, wherein application of the compound or the composition to the    location repels a honeybee from foraging and/or collecting nectar    from a flower of the treated plant.-   80. A method of repelling a honeybee from a structure, the method    comprising the step of applying a honeybee repellent according to    any one of embodiments 1-66 or a composition according to any one of    embodiments 67-74 to a structure or in a location in the vicinity of    the structure, wherein application of the compound or the    composition to the structure repels a honeybee from the structure.-   81. A seed composition comprising a seed and a honeybee repellent    according to any one of embodiments 1-66 or a composition according    to any one of embodiments 67-74.-   82. A seed composition of embodiment 81, wherein the composition    further comprises one or more of an insecticide, a pesticide, a    fungicide, a fertilizer of a micronutrient or macronutrient nature,    a herbicide, a feeding inhibitor, an insect molting inhibitor, an    insect mating inhibitor, an insect maturation inhibitor, a    nematocide, a nutritional or horticultural supplement, a larvicide,    a seed, or any combination thereof-   83. A device comprising a honeybee repellent according to any one of    embodiments 1-66 or a composition according to any one of    embodiments 67-74.

EXAMPLES

The following non-limiting examples are provided for illustrativepurposes only in order to facilitate a more complete understanding ofrepresentative embodiments now contemplated. These examples should notbe construed to limit any of the embodiments described in the presentspecification, including those pertaining to the compounds,compositions, pharmaceutical kits, methods or uses of repellinghoneybees.

Example 1 Testing of Candidate Compounds Using Binding Assay

To identify a honeybee repellent disclosed herein, candidate compoundswere screened based upon the fact that 2-heptanone is an establishedrepellent of bees. 2-heptanone is thought to mediate its behavioralresponse through binding to a specific odorant-binding protein calledOBP2. Therefore compounds that bind OBP2 have the potential to act asodor “mimics” of 2-heptanone. By utilizing a fluorescent-quench,ligand-protein-binding assay, 30,000 compounds from the DIVERSET®library (ChemBridge Corp., San Diego, Calif.), a chemical library, werescreened and over 150 candidate compounds were isolated that bind OBP2(Table 1). Such assays are generally known in the art. See, e.g.,Briand, et al., Ligand-Binding Properties and StructuralCharacterization of a Novel Rat Odorant-Binding Protein Variant, Eur. J.Biochem. 267(10): 3079-3089 (2000); Briand, et al., Ligand Binding andPhysico-Chemical Properties of ASP2, A Recombinant Odorant-BindingProtein From Honeybee (Apis mellifera L.), Eur. J. Biochem. 268(3):752-760 (2001); Briand, et al., Characterization of a ChemosensoryProtein (ASP3c) from Honeybee (Apis mellifera L.) as a Brood PheromoneCarrier, Eur. J. Biochem. 269(18): 4586-4596 (2002), each of which ishereby incorporated by reference in its entirety.

Example 2 Testing of Candidate Compounds Using the PER Assay

To determine whether a living honeybee can recognize a candidatecompound, these compounds were tested using a proboscis extensionresponse (PER) assay using classical conditioning approaches. Proboscisextension response conditioning is a case of appetitive learning, inwhich bees learn to associate odor stimuli with sucrose reward in thelaboratory. In this case, bees were conditioned to produce a PER to2-heptanone as the conditioned stimulus and a sugar reward as theunconditioned stimulus. These trained bees were then exposed to an odorpulse of a candidate compound to test whether a candidate compound wouldalso produce a PER. If the candidate compound “mimics” 2-heptanone thenthe honeybee will extend its proboscis.

For conditioning procedures, Apis mellifera Carniolan foraging workerhoneybees were obtained from a local apiary (typically 60 bees pershipment). The honeybees were held overnight in insect cages with foodand water freely available, in an environmentally controlled room on alight cycle similar to the ambient cycle at the time of the assay.

For conditioning procedures, all tests were done in an odorant deliveryapparatus set inside a fume hood. The apparatus comprised a set ofopen-ended, horizontal, 3 cm diameter by 10 cm long plastic tubes. Eachtube was designed where a honeybee could be positioned at the distal endof a tube, with the opening at the other end of the tube locatedproximal to an inlet of the fume hood. To deliver an odorant, room airwas pumped by a diaphragm pump through a particle filter via 0.25 inchplastic tubing at approximately 0.7 m/sec. The air flow passes into theheadspace above an odorant (0.5% [v/v]2-heptanone dissolved in odorlesslight paraffin oil) contained in a 100 mL bottle. The headspace air thenpasses through another plastic tube to a manifold of 4-way valves, eachof which was attached near the proximal end of a plastic tube containinga bee. Each bee was exposed separately for a desired time period to theodorant by opening and closing the appropriate valve. When each valvewas closed, the odor was flushed away immediately by the continuous fumehood air stream.

To train a honeybee to respond to a conditioned and unconditionedstimuli, bees were placed, without anesthesia, in individual 1.5 mLmicro-centrifuge holding tubes and held overnight without access to foodor water. The holding tubes containing the starved bees were placed inracks in groups of eight. One rack at a time was placed behind theodorant delivery apparatus so that each bee's head is centered at thedistal end of a horizontal plastic tube. Each bee was exposed to the2-heptanone odorant alone for four seconds, and then while being fed an80% sucrose solution for and additional three seconds. The sucrosesolution was delivered on a piece of saturated filter paper held inforceps. The wet paper was touched to the bee's antennae if the bee didnot immediately extend its proboscis (which usually happens in afraction of a second after the sucrose solution comes near the bee'shead). Positive and negative responses were recorded. A positive PER wasscored when a bee extended its proboscis before the sucrose appeared. Ina typical trial, 48 individual bees were subjected to conditioning. Sixrounds of training were done before testing began, and typically amajority of the bees were successfully conditioned by the second orthird round of training.

After conditioning, honeybees were tested with the candidate compoundsthe same day or on the following day or, most commonly, both. When heldovernight, bees were fed with sucrose and kept in their holding tubes.When tested the day after training, bees were given one or more roundsof conditioning with 2-heptatone to refresh their memories. Candidatecompounds stocks were made at 5% (w/v) in polyoxyethylene octyl phenylether (TRITON® X-100), a non-ionic detergent/surfactant, and stored at4° C. This detergent is similar to substances used as carriers for avariety of commercial pest-control agents, can act as a solvent for bothhydrophilic and hydrophobic substances, and is itself nearly odorless.Test solutions were made fresh daily by mixing stock solutions withwater for a final compound concentration of 0.5%. A solution of 0.5%2-heptanone in paraffin oil was used as a positive control. Both waterand 15% polyoxyethylene octyl phenyl ether (TRITON® X-100) in waterserved as negative controls to eliminate false positives.

For candidate compound testing experiments, a single 3 cm length of 3 cmdiameter plastic tube is positioned horizontally in a holder so that airis drawn through it at about 0.7 m/sec. Holding tubes containing atrained honeybee were positioned in racks as for the conditioningprocedure. The rack was then moved sequentially behind the tube so thateach bee's head was directly behind the rear end of tube for the test.The test compounds and controls were presented on a saturated piece offilter paper held at the front end of the 3 cm tube. Bees in each rackwere exposed sequentially to a given candidate compound or control forfour seconds and the results recorded. After bees were tested with onecompound, the process was repeated for the next candidate compound usinga clean tube and testing implements. The order of testing was randomizedfor each day's test and generally 5-6 different candidate compounds weretested in a single day along with 3 controls. Only bees giving a PERwith 2-heptanone, but not with the negative controls were counted incalculating the percent of bees testing positive to each compound (Table2). Generally about half of the total bees subjected to conditioningexhibited a PER with the 2-heptanone positive control, and only a verysmall number of these respond to the negative controls. If a givencohort of bees were tested for two consecutive days, they were testedwith two separate sets of candidate compounds to maximize the number ofindividual bees tested with each compound. In a few cases where a singlecohort of bees was tested twice with the same compounds. In this case,the results were averaged and the average was used in the calculation ofthe percent of positives. Table 2 shows the results from the PER assayfor 66 candidate compounds. Compounds are ranked in order of the percent2-heptanone-positive honeybees that were positive to the test compoundand negative to both water and 15% polyoxyethylene octyl phenyl ether(TRITON® X-100) controls.

TABLE 2 OBP2 Binding and Proboscis Extension Response (PER) Assay2-heptanone 2-heptanone positive bees OBP2 binding Candidate Compoundpositive bees testing positive characteristic of No. Name (N) tocompound compound 7 1-benzyl-4-(4-methoxy-2,3- 57 39.0% Moderatedimethylbenzyl)piperazine 40 2-acetyl-4-chlorophenyl 4- 54 34.3%Moderate methylbenzoate 2 4-[2-(4-nitrophenyl)vinyl]phenol 47 31.5%Moderate 1 1-(4-methoxyphenyl)-3-(2-methyl-1H- 25 26.6% Moderateindol-3-yl)-2-propen-1-one 60 N-[2-(4-chlorophenoxy)ethyl]-5-(3-methyl-12 25.0% Moderate 1-piperazinyl)-2-nitroaniline 364-bromo-N′-[2-(trifluoroacetyl)-1- 56 24.3% Moderatecyclopenten-1-yl]benzohydrazide 50 1-(4-methoxyphenyl)-3-(1-methyl-1H-54 22.2% ND* indol-3-yl)-2-propen-1-one 48N-methyl-N-[(6-nitro-1,3-benzodioxol-5- 82 18.9% ND*yl)methyl]-2-(2-pyridinyl)ethanamine 47 4-[(6-nitro-1,3-benzodioxol-5-82 18.3% ND* yl)methyl]thiomorpholine 53 6-(4-iodophenyl)imidazo[2,1- 1118.2% Moderate b][1,3]thiazole 56 4-{[(9-ethyl-9H-carbazol-3- 11 18.2%Moderate yl)methylene]amino}benzamide 611-[(6-nitro-1,3-benzodioxol-5-yl)methyl]- 35 17.4% Moderate4-phenylpiperazine 57 N-phenyl-N′-[2- 12 16.7% Moderate(phenylethynyl)phenyl]urea 59 methyl 3-[(4-fluorobenzoyl)amino]-2- 1216.7% Moderate butenoate 51 1,1′-(1,4-phenylene)bis[3-(1H-indol-3-yl)-54 14.8% ND* 2-propen-1-one] 261-[(6-nitro-1,3-benzodioxol-5-yl)methyl]- 61 14.8% ND*4-phenylpiperazine 3 3-methoxy-4-(4- 35 14.5% NDnitrophenoxy)benzaldehyde oxime 8 (3-amino-4,6-dimethylthieno[2,3- 4714.4% Moderate b]pyridin-2-yl)(4-chlorophenyl)methanone 372,2,4-trimethyl-1,2-dihydro-6-quinolinyl 3- 56 14.4% Moderatemethoxybenzoate 52 1-(4-biphenylyl)-3-(1H-indol-3-yl)-2- 54 13.9% ND*propen-1-one 55 N′-(4-bromo-5-methyl-2-oxo-1,2-dihydro- 11 13.6%Moderate 3H-indol-3-ylidene)spiro[2.3]hexane-1- carbohydrazide 461-(1,3-benzodioxol-5-ylmethyl)-4-(4,5- 82 12.8% ND*dimethoxy-2-nitrobenzyl)piperazine 451-methyl-4-[(6-nitro-1,3-benzodioxol-5- 82 11.6% ND*yl)methyl]piperazine 62 1-(4-methoxy-2,3-dimethylbenzyl)-4- 35 11.6% NDmethylpiperazine 63 4-(4-methoxy-2,3- 32 10.9% NDdimethylbenzyl)morpholine 9 2-phenyl-4-(2-thienylmethylene)-1,3- 52 9.7%Moderate oxazol-5(4H)-one 54 2-(3-bromophenyl)-2-oxoethyl benzoate 119.1% Moderate 35 4-hydroxy-3-[2-(4-hydroxyphenyl)-2,3- 56 9.0% Moderatedihydro-1,5-benzothiazepin-4-yl]-6- methyl-2H-pyran-2-one 132-{[(2-methoxy-1- 52 8.7% ND naphthyl)methylene]amino}-1H-isoindole-1,3(2H)-dione 33 4-(4-methoxy-2,3- 41 8.5% Low*dimethylbenzyl)morpholine 58 3-[(4-chlorobenzoyl)amino]propyl 4- 12 8.3%Moderate chlorobenzoate 44 methyl 5-{[(4- 76 7.3% Moderatebromophenyl)amino]sulfonyl}-2- chlorobenzoate 55-(4-chlorobenzylidene)-3-(2- 43 7.1% NDmethoxyphenyl)-2-thioxo-1,3-thiazolidin- 4-one 641-(3-chlorophenyl)-4-[(6-nitro-1,3- 58 7.0% Moderatebenzodioxol-5-yl)methyl]piperazine 202-[2-(3,5-dimethyl-1H-pyrazol-1-yl)-6- 45 6.7% Strongphenyl-4-pyrimidinyl]phenol 43 5-(1,3-benzodioxol-5-ylmethylene)-3- 766.6% Moderate (1,5-dimethyl-3-oxo-2-phenyl-2,3-dehydro-1H-pyrazol-4-yl)-2-thioxo-1,3- thiazolidin-4-one 251-(4-methoxy-2,3-dimethylbenzyl)-4- 61 6.6% Low* methylpiperazine 651-(4-methoxybenzyl)-4-(3- 32 6.3% ND methylbenzyl)piperazine 161-butyl-4-hydroxy-2-oxo-N-(2- 73 6.2% Strongpyridinylmethyl)-1,2-dihydro-3- quinolinecarboxamide 17(4-bromophenyl)(5-methoxy-2-methyl-1- 73 6.2% Strongbenzofuran-3-yl)methanone 12 (4-bromo-3-chlorophenyl)(4- 52 5.8% NDethoxybenzylidene)amine 27 1-benzyl-4-(4-methoxy-3- 35 5.8% Low*methylbenzyl)piperazine 34 1-(4-methoxybenzyl)-4-(3- 41 4.9% ND*methylbenzyl)piperazine 38 N′-[(2- 41 4.9% Moderatechlorobenzoyl)oxy]benzenecarboximidamide 10 2-(benzoylamino)-N-(2- 524.8% Moderate chlorophenyl)benzamide 111-(4-bromobenzoyl)-2,2,4-trimethyl-1,2- 52 4.8% Moderatedihydroquinoline 24 1-(3-chlorophenyl)-4-[(6-nitro-1,3- 84 4.8% NDbenzodioxol-5-yl)methyl]piperazine 4 dimethyl2-(1,2,2-trimethyl-3-thioxo-2,3- 43 4.7% NDdihydro-4(1H)-quinolinylidene)-1,3- dithiole-4,5-dicarboxylate 21 ethyl2-(3-aminophenyl)-4- 45 4.4% Strong quinolinecarboxylate 221,2,3-trichloro-4-(isopropylamino)anthra- 45 4.4% Strong 9,10-quinone 153-ethyl-5-(4-hydroxybenzylidene)-2- 73 4.1% Strongthioxo-1,3-thiazolidin-4-one 18 3-{2-[(4-fluorobenzyl)amino]phenyl}- 734.1% Strong 2(1H)-quinoxalinone 14 4-[4-nitro-3-(2- 52 3.9% Moderatephenoxyethoxy)phenyl]morpholine 23[1-(3-nitrobenzyl)-3-piperidinyl]methyl 3- 45 3.3% Strong phenylacrylate66 N-(4-methoxy-2,3-dimethylbenzyl)- 32 3.1% NDN,N′,N′-trimethyl-1,2-ethanediamine 19 dimethyl2-(2,2,7-trimethyl-3-thioxo-2,3- 73 2.8% Strongdihydro-4(1H)-quinolinylidene)-1,3- dithiole-4,5-dicarboxylate 422,6-di-tert-butylbenzo-1,4-quinone 4- 76 2.6% Moderate thiosemicarbazone32 N-(4-methoxy-2,3-dimethylbenzyl)- 41 2.4% ND*N,N′,N′-trimethyl-1,2-ethanediamine 39 N-benzyl-2-phenyl-N-(3- 54 1.9%Moderate pyridinylmethyl)ethanamine 41 ethyl methyl4-(4-bromophenyl)-2,6- 72 1.4% Moderate dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate 6 7-(diethylamino)-4-methyl-3-nitro-2H- 43 0.0 NDchromen-2-one 28 1-(4-methoxy-2,3-dimethylbenzyl)-4-(3- 35 0.0 Low*phenyl-2-propen-1-yl)piperazine 291-(2,3-dimethylphenyl)-4-(4-methoxy-2,3- 35 0.0 Low*dimethylbenzyl)piperazine 30 1-(4-methoxy-2,3-dimethylbenzyl)-4- 35 0.0ND* phenylpiperazine 31 2-[4-(4-methoxy-2,5-dimethylbenzyl)-1- 35 0.0ND* piperazinyl]ethanol 49 1-(4-methoxy-2,3-dimethylbenzyl)-4-(4- 54 0.0ND* methylphenyl)piperazine ND, not determined. Low, indicates nodetectable binding to OBP2. Moderate, indicates that 50% or less of thecompound bound to OBP2. Strong, indicates that 51% or more of thecompound bound to OBP2. *Compound selected by in silico analysis.

Example 3 Testing of Candidate Compounds Using Choice Test

To determine whether living honeybees will choice to move towards asource of a candidate compound, these compounds were assayed using achoice test in a free-flight box apparatus.

All tests were done in a free-flight box apparatus. The apparatuscomprises a 244 cm long×46 cm deep×30 cm high clear plastic boxincluding two equally-sized independent testing chambers, each with 10cm diameter air inlets that admit filtered room air, separated by asmaller central chamber with a screened air outlet to each testingchamber. Air can be pulled through the sealed box via a 10 cm diameterduct from the air outlet using an AQE Fume Fighter 500 fume extractor(BPA Air Quality Solutions, LLC, Charleston, S.C.), which removes thetest odors using activated charcoal and HEPA filters. The box is housedin an environmentally controlled room with overhead illumination timedto correspond to the current ambient light cycle including 2 additionalsets of lights timed to approximate crepuscular lighting conditions. Thebottom of the apparatus was lined with clean absorbent paper marked witha 4×9 grid pattern, forming 12 cm×12 cm squares with marked coordinates.

Apis mellifera Carniolan foraging worker honeybees were obtained from alocal apiary (typically 60 bees per shipment). Thirty honeybees were putinto each testing chamber and were allowed to acclimate for 24 hourswith food and water freely available.

At the beginning of each test day all food was removed from the testchamber, but water was continually available throughout all tests. Foreach test, approximately 0.3 g of organic, raw orange blossom honey wasadded to each clean small plastic weigh boat (Cole-Palmer). The honeyboats were placed in small plastic culture dishes, which weredistributed in the marked squares in the chambers. The positions of thedishes on the grid for a set of trials was chosen to avoid the bees'preferred resting area so that they had to find the food actively, butthe same dish positions were maintained for a given set of trials. Weused seven dishes of honey: six to which the bees had access and aseventh that had a screened lid. The honey in each boat was weighed onan analytical balance before and after the test, with the screenedsample as a control for evaporative loss. The fume extractor was leftoff during the experimental trails, and was turned on to clear the airafter the test dishes were covered and removed from the chamber at theend of each trial.

Based on the observation that bees tend to return to dishes in the sameposition where they have fed before, each set of trials with each groupof bees began with “Pattern Identification” tests to see which disheslose the most weight, reflecting the most feeding. Once bees wereconsuming an acceptable amount in 10-15 min, typically in 1-2 trials, webegan a set of test compound trials. The test compound was pipetted ontopieces of filter paper placed on the dish bottom below the boatcontaining a fresh, weighed honey sample so that the test compound wasinaccessible to the bees. We used 2 μL of a candidate compound at aconcentration of 0.05-0.5%, in Triton X-100 or paraffin oil, on each offour pieces of filter paper per dish. The test-solution dishes were setat the same positions as the one or two dishes favored in the precedingPattern Identification trial. To eliminate interference from thesolvent, the other dishes without the test substance contained the samevolume of the appropriate solvent on filter papers as the test solutiondishes. The bees were allowed to feed for 10-15 minutes. Bee movementswere recorded by a small, wide-angle digital video camcorder (HD Hero960; GoPro, Halfmoon Bay, Calif.) placed on a tripod in front of thetest chamber. The bees were given a brief rest while the honey wasweighed and a second test was begun with fresh dishes, except that thetest compound-containing dish or dishes were placed at whicheverpositions were most visited in the preceding test. Tests were continueduntil the bees' feeding slowed significantly, typically in 2-4 trials.The bees were then rested for 1-3 hours and a subsequent set of trialsbegun with another Pattern Identification. Tests were performed in bothchambers simultaneously, with the same test compounds. Groups of beescan perform as many as nine tests in one day, with an average of aboutseven on the first day and somewhat fewer on subsequent days, usuallyfor three days.

The results of the free-flight choice tests are shown in Table 3. Tovalidate the test system, the known honeybee repellent, 2-heptanone, atthe concentration used in the PER assays was used as a positive controlfor repellency. In addition, neroli oil, a component of commercialhoneybee attractants (swarm lures), was used as a positive control foran attractant. Lastly, a dish containing food alone was used as acontrol for the components in the solution minus the candidate compound.Candidate compounds with high PER scores as well as compounds with lowerPER scores to examined in order to correlated the results from thechoice test. Using the criterion of reduction of feeding at dishes thatwere most visited in the preceding test, candidate compounds with highPER scores attracted honeybees as well as, or better, than 2-heptanoneas repellents (Table 3), while weaker performers in the PER assay weregenerally less effective repellents. The attractant effect of neroli oilwas also detectable, and one of the weak PER compounds (No. 8) actuallyscored as slightly attractive (Table 3). Two of the candidate compounds(Nos. 2 and 26) were significantly more effective when tested at a10-fold lower concentration (Table 3).

TABLE 3 Choice Tests In Free-Flight Box Apparatus Quintile Number RankCandidate Compound % Positive trials/bee Repellence Change No. NameAmount in PER groups Score¹ Score² — 2-heptanone 0.5% —  56/12 54.6%−2.73 — Neroli oil 0.5% — 16/3  −65% 3.88 — No compound 0 — 1937/46  —−0.31 7 1-benzyl-4-(4-methoxy-2,3- 0.1% 39.0 30/8 62.0% −3.10dimethylbenzyl)piperazine 2 4-[2-(4-nitrophenyl)vinyl]phenol 0.5% 31.533/8 37.6% −1.88 0.05%  ND 17/5 57.7% −2.88 40 2-acetyl-4-chlorophenyl4- 0.5% 30.5 19/8 54.6% −2.25 methylbenzoate 11-(4-methoxyphenyl)-3-(2-methyl- 0.5% 26.6  42/12 57.8% −2.891H-indol-3-yl)-2-propen-1-one 36 4-bromo-N′−[2-(trifluoroacetyl)-1- 0.5%24.3 15/7 56.3% −2.65 cyclopenten-1-yl]benzohydrazide 501-(4-methoxyphenyl)-3-(1-methyl- 0.5% 22.2  4/2 55.7% −2.331H-indol-3-yl)-2-propen-1-one 26 1-[(6-nitro-1,3-benzodioxol-5- 0.5%14.8 30/7 58.6% −2.93 yl)methyl]-4-phenylpiperazine 0.05%  ND 26/7 60.0%−3.00 3 3-methoxy-4-(4- 0.5% 14.5  23/11 49.8% −1.4nitrophenoxy)benzaldehyde oxime 8 (3-amino-4,6-dimethylthieno[2,3- 0.5%14.4  6/3 −10.7%   1.05 b]pyridin-2-yl)(4- chlorophenyl)methanone 92-phenyl-4-(2-thienylmethylene)-1,3- 0.5% 9.7 15/6 43.3% −1.13oxazol-5(4H)-one 10 2-(benzoylamino)-N-(2- 0.5% 4.8 25/6 45.6% −1.28chlorophenyl)benzamide ¹Repellence Score is the percent food-weightchange in dishes containing the test molecule, compared to correspondingdishes in the preceding test, averaged over all of the tests (a negativescore = an increase in food consumption). ²Quintile Rank Change Score iscalculated by ranking the weight of food eaten in each dish as a percentof total food in all dishes in quintiles (1 = most food eaten), thensubtracting the rank of each dish containing the test compound in onetest run from the rank of the corresponding dish in the preceding testand averaging over all of the tests. A negative score indicates adecrease in food eaten; a positive score indicates an increase in foodeaten. ND, not determined.

Example 4 Use of Honeybee Repellent in Conjunction with Insecticide

This example illustrates how to use a honeybee repellent disclosedherein to repel honeybees from an area where insecticides have also beenapplied in order to reduce honeybee mortality and avoid insecticidecontamination of honey, beeswax, and other hive products.

At the start of a growing season, an almond tree grower delays the useof a nicotine-based insecticide like Clothianidin and Imidacloprid inorder to minimize harmful effects of this insecticide on honeybees whilethese insects enter his almond tree orchards. While gathering nectarfrom the flowers of the almond trees, the honeybees pollinate the trees.Subsequently the grower does apply a nicotine-based insecticide likeClothianidin and Imidacloprid to his orchards. At the same or similartime, the grower also applies a honeybee repellent disclosed herein. Thegrower may periodically applies the repellant using the same schedule asthat for the insecticide, or one based on the half-life of the honeybeerepellent. The grower realizes typical yields of almonds, while at thesame time his neighbor, who is a beekeeper, reports that his beecolonies are healthy and he has harvested an excellent yield of honey.

Example 5 Use of Honeybee Repellent to Increase Yields of Seedless Crops

This example illustrates how to use a honeybee repellent disclosedherein to prevent unwanted pollination of crop plants by honeybees wheresuch pollination reduces the market value due to the resulting seededcrop.

At the start of a growing season, a mandarin orange grower applies anicotine-based insecticide like Clothianidin and Imidacloprid. At thesame or similar time, the grower also applies a honeybee repellentdisclosed herein. The grower may periodically applies the repellantusing the same schedule as that for the insecticide, or one based on thehalf-life of the honeybee repellent. The grower realizes excellentyields of seedless mandarin oranges. A beekeeper nearby reports that hisbee colonies are healthy.

Example 6 Use of Honeybee Repellent to Increase Yields of Seedless Crops

This example illustrates how to use a honeybee repellent disclosedherein to prevent unwanted pollination of crop plants by honeybees wheresuch pollination reduces the market value due to the resulting seededcrop.

At the start of a growing season, a tangerine grower applies a honeybeerepellent disclosed herein. The grower may periodically apply therepellant based on its half-life. The grower realizes excellent yieldsof seedless tangerine. A beekeeper nearby reports that his bee coloniesare healthy.

Example 7 Use of Honeybee Repellent to Control Honeybee Presence inOutdoor Area

This example illustrates how to use a honeybee repellent disclosedherein to keep away honeybees from outdoor areas where human activitiesare occurring and would be disrupted by honeybee presence, such as,e.g., an outdoor activity like a sporting event or picnic.

At the start of a Fourth of July picnic, a mother applies a honeybeerepellent disclosed herein in the area where her family is setting uptable and grill. The mother realizes that, unlike previous events ofthis nature, honeybees did not seem to bother her family while they wereeating their lunch.

Example 8 Use of Honeybee Repellent to Control Honeybee Presence inStructure

This example illustrates how to use a honeybee repellent disclosedherein to keep away honeybees from man-made structures in order toprevent infestation of a colony, such as, e.g., a commercial building, ahouse, a shed, or other structure.

A man recently had an exterminator remove a bee colony that establisheda hive inside one of the ways of his house. This was a reoccurringproblem as it had happened three previous two years as well. Afterremoval, the exterminator applied a honeybee repellent disclosed hereinand also explained to the homeowner that he should periodically applythe repellent in order to prevent a further infestation. The homeownerdid as instructed. The next year honeybees did not establish a hive inthe man's house.

In closing, it is to be understood that although aspects of the presentspecification are highlighted by referring to specific embodiments, oneskilled in the art will readily appreciate that these disclosedembodiments are only illustrative of the principles of the subjectmatter disclosed herein. Therefore, it should be understood that thedisclosed subject matter is in no way limited to a particularmethodology, protocol, and/or reagent, etc., described herein. As such,various modifications or changes to or alternative configurations of thedisclosed subject matter can be made in accordance with the teachingsherein without departing from the spirit of the present specification.Lastly, the terminology used herein is for the purpose of describingparticular embodiments only, and is not intended to limit the scope ofthe present invention, which is defined solely by the claims.Accordingly, the present invention is not limited to that precisely asshown and described.

Certain embodiments of the present invention are described herein,including the best mode known to the inventors for carrying out theinvention. Of course, variations on these described embodiments willbecome apparent to those of ordinary skill in the art upon reading theforegoing description. The inventor expects skilled artisans to employsuch variations as appropriate, and the inventors intend for the presentinvention to be practiced otherwise than specifically described herein.Accordingly, this invention includes all modifications and equivalentsof the subject matter recited in the claims appended hereto as permittedby applicable law. Moreover, any combination of the above-describedembodiments in all possible variations thereof is encompassed by theinvention unless otherwise indicated herein or otherwise clearlycontradicted by context.

Groupings of alternative embodiments, elements, or steps of the presentinvention are not to be construed as limitations. Each group member maybe referred to and claimed individually or in any combination with othergroup members disclosed herein. It is anticipated that one or moremembers of a group may be included in, or deleted from, a group forreasons of convenience and/or patentability. When any such inclusion ordeletion occurs, the specification is deemed to contain the group asmodified thus fulfilling the written description of all Markush groupsused in the appended claims.

Unless otherwise indicated, all numbers expressing a characteristic,item, quantity, parameter, property, term, and so forth used in thepresent specification and claims are to be understood as being modifiedin all instances by the term “about.” As used herein, the term “about”means that the characteristic, item, quantity, parameter, property, orterm so qualified encompasses a range of plus or minus ten percent aboveand below the value of the stated characteristic, item, quantity,parameter, property, or term. Accordingly, unless indicated to thecontrary, the numerical parameters set forth in the specification andattached claims are approximations that may vary. At the very least, andnot as an attempt to limit the application of the doctrine ofequivalents to the scope of the claims, each numerical indication shouldat least be construed in light of the number of reported significantdigits and by applying ordinary rounding techniques. Notwithstandingthat the numerical ranges and values setting forth the broad scope ofthe invention are approximations, the numerical ranges and values setforth in the specific examples are reported as precisely as possible.Any numerical range or value, however, inherently contains certainerrors necessarily resulting from the standard deviation found in theirrespective testing measurements. Recitation of numerical ranges ofvalues herein is merely intended to serve as a shorthand method ofreferring individually to each separate numerical value falling withinthe range. Unless otherwise indicated herein, each individual value of anumerical range is incorporated into the present specification as if itwere individually recited herein.

The terms “a,” “an,” “the” and similar referents used in the context ofdescribing the present invention (especially in the context of thefollowing claims) are to be construed to cover both the singular and theplural, unless otherwise indicated herein or clearly contradicted bycontext. All methods described herein can be performed in any suitableorder unless otherwise indicated herein or otherwise clearlycontradicted by context. The use of any and all examples, or exemplarylanguage (e.g., “such as”) provided herein is intended merely to betterilluminate the present invention and does not pose a limitation on thescope of the invention otherwise claimed. No language in the presentspecification should be construed as indicating any non-claimed elementessential to the practice of the invention.

Specific embodiments disclosed herein may be further limited in theclaims using consisting of or consisting essentially of language. Whenused in the claims, whether as filed or added per amendment, thetransition term “consisting of” excludes any element, step, oringredient not specified in the claims. The transition term “consistingessentially of” limits the scope of a claim to the specified materialsor steps and those that do not materially affect the basic and novelcharacteristic(s). Embodiments of the present invention so claimed areinherently or expressly described and enabled herein.

All patents, patent publications, and other publications referenced andidentified in the present specification are individually and expresslyincorporated herein by reference in their entirety for the purpose ofdescribing and disclosing, for example, the compositions andmethodologies described in such publications that might be used inconnection with the present invention. These publications are providedsolely for their disclosure prior to the filing date of the presentapplication. Nothing in this regard should be construed as an admissionthat the inventors are not entitled to antedate such disclosure byvirtue of prior invention or for any other reason. All statements as tothe date or representation as to the contents of these documents isbased on the information available to the applicants and does notconstitute any admission as to the correctness of the dates or contentsof these documents.

The invention claimed is:
 1. A method of repelling a honeybee from alocation or a structure or a plant, the method comprising the step ofapplying a honeybee repellent to the location, the structure, the plantand/or in a vicinity nearby the location, the structure, or the plant,wherein application of the honeybee repellent to the location, thestructure or the plant repels a honeybee from the location, thestructure, or the plant, wherein the honeybee repellent has a structureof formula XIIIa:

wherein X is C, N, O or S; Z is C or N; R¹ is selected from H, OH, C₁₋₆alkyl, OC₁₋₆ alkyl, CO₂C₁₋₆ alkyl, halogen, NO₂, or SO₂; and R² isselected from C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₆ cycloalkyl,C₂₋₆ cycloalkenyl, C₂₋₆ cycloalkynyl, optionally substituted alkylaryl,optionally substituted arylalkyl, alkoxy, optionally substitutedaryloxy, optionally substituted arylalkoxy, optionally substitutedalkoxyalkylaryl, heteroalkyl, optionally substituted heteroaryl,optionally substituted heteroarylalkyl, cyclic heteroalkyl, cyclicheteroalkylalkyl, acyl, optionally substituted benzoyl, optionallysubstituted 2-benzoylethenyl, OH, OR⁵, CN, OCF₃, CF₃, Br, Cl, F,alkylcarbonyl, morpholino, piperidinyl, dioxanyl, pyranyl, optionallysubstituted heteroaryl, furanyl, thiophenyl, tetrazole, thiazole,isothiazole, imidazole, thiadiazole, thiadiazole S-oxide, thiadiazoleS,S-dioxide, sulfonylamidine, sulfonylguanidine, sulfamoylamidine,sulfamoylguanidine, pyrazole, oxazole, isoxazole, pyridinyl,pyrimidinyl, piperazine, quinoline, isoquinoline; R⁵ is eachindependently H, OH, C₁₋₆ alkyl, OC₁₋₆ alkyl, OC₁₋₆ cycloalkyl, CO₂C₁₋₆alkyl, CO₂C₁₋₆ cycloalkyl, halogen, NO₂, or SO₂; and m is 0 to
 5. 2. Themethod of claim 1, wherein the honeybee repellent has a structure offormula XIIIa:

wherein X is N, O or S; Z is C; R¹ is selected from OH, C₁₋₆ alkyl,OC₁₋₆ alkyl, CO₂C₁₋₆ alkyl, halogen, NO₂, or SO₂; R² is selected fromC₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₆ cycloalkyl, C₂₋₆cycloalkenyl, C₂₋₆ cycloalkynyl, optionally substituted alkylaryl,optionally substituted arylalkyl, alkoxy, optionally substitutedaryloxy, optionally substituted arylalkoxy, optionally substitutedalkoxyalkylaryl, acyl, optionally substituted benzoyl, optionallysubstituted 2-benzoylethenyl, OH, OR⁵, CN, OCF₃, CF₃, Br, Cl, F,alkylcarbonyl, morpholino, piperidinyl, dioxanyl, pyranyl, optionallysubstituted heteroaryl, furanyl, thiophenyl, tetrazole, thiazole,isothiazole, imidazole, thiadiazole, thiadiazole S-oxide, thiadiazoleS,S-dioxide, sulfonylamidine, sulfonylguanidine, sulfamoylamidine,sulfamoylguanidine, pyrazole, oxazole, isoxazole, pyridinyl,pyrimidinyl, piperazine, quinoline, isoquinoline; R⁵ is eachindependently H, OH, C₁₋₆ alkyl, OC₁₋₆ alkyl, OC₁₋₆ cycloalkyl, halogen;and m is 0 to
 2. 3. The method of claim 1, wherein the honeybeerepellent is an optionally substituted1-(4-methoxyphenyl)-3-(2-methyl-1H-indol-3-yl)-2-propen-1-one (Compound1), an optionally substituted1-(4-methoxyphenyl)-3-(1-methyl-1H-indol-3-yl)-2-propen-1-one (Compound50), an optionally substituted(4-bromophenyl)(5-methoxy-2-methyl-1-benzofuran-3-yl)methanone (Compound17) or any combination thereof.
 4. The method of claim 3, wherein thehoneybee repellent is1-(4-methoxyphenyl)-3-(2-methyl-1H-indol-3-yl)-2-propen-1-one,1-(4-methoxyphenyl)-3-(1-methyl-1H-indol-3-yl)-2-propen-1-one,(4-bromophenyl)(5-methoxy-2-methyl-1-benzofuran-3-yl)methanone or anycombination thereof.
 5. The method of claim 3, wherein the honeybeerepellent has a structure according to any one of the followingformulae:


6. The method of claim 1, wherein the repelling a honeybee from alocation or a structure or a plant prevents the honeybee from foragingand/or collecting nectar.
 7. The method of claim 1, wherein applicationof the honeybee repellent to the location, the structure, the plantand/or in the vicinity nearby the location, the structure, or the plantis achieved using a seed composition that is coated with the honeybeerepellent.
 8. The method of claim 1, wherein application of the honeybeerepellent to the location, the structure, the plant and/or in thevicinity nearby the location, the structure, or the plant is achievedusing a device comprising the honeybee repellent.